Mechanisms of tumor cell extravasation in an in vitro microvascular network platform
Open accessAbstract
A deeper understanding of the mechanisms of tumor cell extravasation is essential in creating therapies that target this crucial step in cancer metastasis. Here, we use a microfluidic platform to study tumor cell extravasation from in vitro microvascular networks formed via vasculogenesis. We demonstrate tight endothelial cell-cell junctions, basement membrane deposition and physiological values of vessel permeability. Employing our assay, we demonstrate impaired endothelial barrier function and increased extravasation efficiency with inflammatory cytokine stimulation, as well as positive correlations between the metastatic potentials of MDA-MB-231, HT-1080, MCF-10A and their extravasation capabilities. High-resolution time-lapse microscopy reveals the highly dynamic nature of extravasation events, beginning with thin tumor cell protrusions across the endothelium followed by extrusion of the remainder of the cell body through the formation of small (~1 μm) openings in the endothelial barrier which grows in size (~8 μm) to allow for nuclear transmigration. No disruption to endothelial cell-cell junctions is discernible at 60×, or by changes in local barrier function after completion of transmigration. Tumor transendothelial migration efficiency is significantly higher in trapped cells compared to non-trapped adhered cells, and in cell clusters versus single tumor cells.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Microvascular networks are a dramatic improvement over previous 2D extravasation models such as Boyden Transwell-chambers because transwells do not allow dynamic high-resolution single-cell imaging and microvascular networks better replicate 3D vessel architecture and endothelial barrier function.
“These µVNs represent a dramatic improvement over previous 2D extravasation models such as Boyden Transwell-chambers that consist of ECs seeded onto a permeable membrane inserted in a well-plate, since transwells do not allow for dynamic high resolution single cell imaging due to the long distance of the insert from the objective.”
From Microfluidics: A New Tool for Modeling Cancer–Immune Interactions (2016) · cites this paper as [21]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredRecent studies increasingly use microvascular networks whose permeability, architecture and diameters are more similar to in vivo microvascular beds.
“Recent studies are increasingly employing microvascular networks (µVNs)[21, 23, 24], where the permeability, architecture and diameters of vessels are more similar to those found in in vivo microvascular beds (Figure 2A) [21].”
From Microfluidics: A New Tool for Modeling Cancer–Immune Interactions (2016) · cites this paper as [21]
The Introduction describes recent development of perfusable 3D microvascular networks with a more physiologically relevant configuration, and the Discussion says their permeability is comparable to that of in vivo venules. The Results describe self-organized vessels with 8–96 μm lumens, but our copy does not compare those diameters with in vivo microvascular beds. (LLM, conf=0.83)
Experimental — accuracy not yet measuredSelf-assembly models for extravasation have been developed and used extensively.
“Self-assembly models for extravasation have been developed and used extensively (Figure 3I) [83,84].”
From Cancer-on-chip models for metastasis: importance of the tumor microenvironment (2024) · cites this paper as [83]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Mantovani, A., Allavena, P., Sica, A., & Balkwill, F. (2008) · Nature · doi:10.1038/nature07205 · Cited by 11,399 · see citing works
The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited
Fidler, I. J. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1098 · Cited by 4,686 · see citing works
Isolation of rare circulating tumour cells in cancer patients by microchip technology
Nagrath, S., Sequist, L. V. D., Maheswaran, S., Bell, D. W., Irimia, D., Ulkus, L., Smith, M. R., Kwak, E. L., Digumarthy, S. R., Muzikansky, A., et al. (2007) · Nature · doi:10.1038/nature06385 · Cited by 3,565 · see citing works
Multistep Nature of Metastatic Inefficiency
Luzzi, K. J., MacDonald, I. C., Schmidt, E. E., Kerkvliet, N. I., Morris, V. L., Chambers, A. F., & Groom, A. C. (1998) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65628-3 · Cited by 1,246 · see citing works
Real-time imaging reveals the single steps of brain metastasis formation.
Kienast, Y., von Baumgarten, L., Fuhrmann, M., Klinkert, W. E. F., Goldbrunner, R., Herms, J., & Winkler, F. (2010) · Nature Medicine · doi:10.1038/nm.2072 · Cited by 1,138 · see citing works
In vitro microvessels for the study of angiogenesis and thrombosis
Zheng, Y., Chen, J., Craven, M., Choi, N. W., Totorica, S., Diaz-Santana, A., Kermani, P., Hempstead, B., Fischbach-Teschl, C., López, J. A., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1201240109 · Cited by 894 · see citing works
In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment
Sipkins, D. A., Wei, X., Wu, J. W., Runnels, J. M., Côté, D. C., Means, T. K., Luster, A. D., Scadden, D. T., & Lin, C. P. (2005) · Nature · doi:10.1038/nature03703 · Cited by 880 · see citing works
Three-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function
Zervantonakis, I. K., Hughes-Alford, S. K., Charest, J. L., Condeelis, J. S., Gertler, F. B., & Kamm, R. D. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1210182109 · Cited by 872 · see citing works
Self-citationEngineering of functional, perfusable 3D microvascular networks on a chip
Kim, S., Lee, H., Chung, M., & Jeon, N. L. (2013) · Lab on a Chip · doi:10.1039/c3lc41320a · Cited by 872 · see citing works
Al‐Mehdi, A., Tozawa, K., Fisher, A. B., Shientag, L., Lee, A., & Muschel, R. J. (2000) · Nature Medicine · doi:10.1038/71429 · Cited by 706 · see citing works
Qian, B., Deng, Y., Im, J. H., Muschel, R. J., Zou, Y., Li, J., Lang, R. A., & Pollard, J. W. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006562 · Cited by 664 · see citing works
Microfluidic assay for simultaneous culture of multiple cell types on surfaces or within hydrogels
Shin, Y., Han, S., Jeon, J. S., Yamamoto, K., Zervantonakis, I. K., Sudo, R., Kamm, R. D., & Chung, S. (2012) · Nature Protocols · doi:10.1038/nprot.2012.051 · Cited by 617 · see citing works
Self-citationColmone, A. C., de Amorim, M. G., Pontier, A. L., Wang, S., Jablonski, E. M., & Sipkins, D. A. (2008) · Science · doi:10.1126/science.1164390 · Cited by 605 · see citing works
Illuminating the metastatic process
Sahai, E. A. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2229 · Cited by 566 · see citing works
Breaching multiple barriers: leukocyte motility through venular walls and the interstitium
Nourshargh, S., Hordijk, P. L., & Sixt, M. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2889 · Cited by 561 · see citing works
Formation of perfused, functional microvascular tubes in vitro
Chrobak, K. M., Potter, D. R., & Tien, J. (2006) · Microvascular Research · doi:10.1016/j.mvr.2006.02.005 · Cited by 555 · see citing works
ErbB2, but not ErbB1, reinitiates proliferation and induces luminal repopulation in epithelial acini
Muthuswamy, S. K., Li, D., Lelièvre, S. A., Bissell, M. J., & Brugge, J. S. (2001) · Nature Cell Biology · doi:10.1038/ncb0901-785 · Cited by 554 · see citing works
Fluid forces control endothelial sprouting
Song, J. W., & Munn, L. L. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1105316108 · Cited by 498 · see citing works
Weis, S. M., Cui, J., Barnes, L. A., & Cheresh, D. A. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200408130 · Cited by 477 · see citing works
Haraldsen, G., Kvale, D., LIEN, B., Farstad, I. N., & Brandtzaeg, P. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.156.7.2558 · Cited by 425 · see citing works
Role of the cytoskeleton during leukocyte responses
Vicente‐Manzanares, M., & Sánchez‐Madrid, F. (2004) · Nature reviews. Immunology · doi:10.1038/nri1268 · Cited by 360 · see citing works
Visualizing extravasation dynamics of metastatic tumor cells
Stoletov, K. V., Kato, H., Zardouzian, E., Kelber, J. A., Yang, J., Shattil, S. J., & Klemke, R. L. (2010) · Journal of Cell Science · doi:10.1242/jcs.069443 · Cited by 334 · see citing works
High-resolution imaging of the dynamic tumor cell–vascular interface in transparent zebrafish
Stoletov, K. V., Montel, V., Lester, R. D., Gonias, S. L., & Klemke, R. L. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703446104 · Cited by 324 · see citing works
Microfluidic Endothelium for Studying the Intravascular Adhesion of Metastatic Breast Cancer Cells
Song, J. W., Cavnar, S. P., Walker, A. C., Luker, K. E., Gupta, M., Tung, Y.-C., Luker, G. D., & Takayama, S. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005756 · Cited by 317 · see citing works
Seeding and Propagation of Untransformed Mouse Mammary Cells in the Lung
Podsypanina, K., Du, Y. N., Jechlinger, M., Beverly, L. J., Hambardzumyan, D., & VARMUS, H. E. (2008) · Science · doi:10.1126/science.1161621 · Cited by 300 · see citing works
Stepping out of the flow: capillary extravasation in cancer metastasis
Miles, F. L., Pruitt, F. L., van Golen, K. L., & Cooper, C. R. (2007) · Clinical & Experimental Metastasis · doi:10.1007/s10585-007-9098-2 · Cited by 263 · see citing works
Hendrix, M. J. C., Seftor, E. A., Seftor, R. E. B., & Fidler, I. J. (1987) · Cancer Letters · doi:10.1016/0304-3835(87)90209-6 · Cited by 240 · see citing works
In vitro model of tumor cell extravasation
Jeon, J. S., Zervantonakis, I. K., Chung, S., Kamm, R. D., & Charest, J. L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0056910 · Cited by 233 · see citing works
Self-citationMcDonald, B., Spicer, J. D., Giannais, B., Fallavollita, L., Brodt, P., & Ferri, L. E. (2009) · International Journal of Cancer · doi:10.1002/ijc.24409 · Cited by 222 · see citing works
Zijlstra, A., Mellor, R. L., Panzarella, G., Aimes, R. T., Hooper, J. D., Marchenko, N. D., & Quigley, J. P. (2002) · PubMed · Cited by 207 · see citing works
Teo, G. S. L., Ankrum, J. A., Martinelli, R., Boetto, S. E., Simms, K., Sciuto, T. E., Dvořàk, A. M., Karp, J. M., & Carman, C. V. (2012) · Stem Cells · doi:10.1002/stem.1198 · Cited by 196 · see citing works
Dormancy of Solitary Metastatic Cells
Townson, J. L., & Chambers, A. F. (2006) · Cell Cycle · doi:10.4161/cc.5.16.2864 · Cited by 182 · see citing works
Non-invasive measurement of solute permeability in cerebral microvessels of the rat
Yuan, W., Lv, Y., Zeng, M., & Fu, B. M. (2008) · Microvascular Research · doi:10.1016/j.mvr.2008.08.004 · Cited by 175 · see citing works
Koop, S., Khokha, R., Schmidt, E. E., MacDonald, I. C., Morris, V. L., Chambers, A. F., & Groom, A. C. (1994) · PubMed · Cited by 157 · see citing works
Crissman, J. D., Hatfield, J. S., Menter, D. G., Sloane, B. F., & Honn, K. V. (1988) · PubMed · Cited by 156 · see citing works
Metastatic tumor cell interactions with endothelium, basement membrane and tissue
Nicolson, G. L. (1989) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(89)90073-2 · Cited by 156 · see citing works
A microfluidic-based device for study of transendothelial invasion of tumor aggregates in realtime
Zhang, Q., Liu, T., & Qin, J. (2012) · Lab on a Chip · doi:10.1039/c2lc00030j · Cited by 151 · see citing works
Sheikh, S., Rainger, G. E., Gale, Z., Rahman, M., & Nash, G. B. (2003) · Blood · doi:10.1182/blood-2003-01-0080 · Cited by 131 · see citing works
CD44v4 Is a Major E-Selectin Ligand that Mediates Breast Cancer Cell Transendothelial Migration
Zen, K., Liu, D.-Q., Guo, Y.-L., Wang, C., Shan, J., Fang, M. L., Zhang, C., & Liu, Y. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001826 · Cited by 128 · see citing works
Multi-step microfluidic device for studying cancer metastasis
Chaw, K. C., Manimaran, M., Tay, E. H., & Swaminathan, S. (2007) · Lab on a Chip · doi:10.1039/b707399m · Cited by 125 · see citing works
Full range physiological mass transport control in 3D tissue cultures
Hsu, Y., Moya, M. L., Abiri, P., Hughes, C. C. W., George, S. C., & Lee, A. P. (2012) · Lab on a Chip · doi:10.1039/c2lc40787f · Cited by 125 · see citing works
Cancer Cells Regulate Biomechanical Properties of Human Microvascular Endothelial Cells
Mierke, C. T. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.256172 · Cited by 118 · see citing works
Koop, S., Schmidt, E. E., MacDonald, I. C., Morris, V. L., Khokha, R., Grattan, M., Leone, J., Chambers, A. F., & Groom, A. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.20.11080 · Cited by 111 · see citing works
Mechanisms by which E-Selectin Regulates Diapedesis of Colon Cancer Cells under Flow Conditions
Tremblay, P., Huot, J., & Auger, F. A. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1229 · Cited by 111 · see citing works
Molecular events during leukocyte diapedesis
Petri, B., & Bixel, M. G. (2006) · FEBS Journal · doi:10.1111/j.1742-4658.2006.05439.x · Cited by 104 · see citing works
Mak, M., Reinhart‐King, C. A., & Erickson, D. (2012) · Lab on a Chip · doi:10.1039/c2lc41117b · Cited by 104 · see citing works
Measurement of individual cell migration parameters for human tissue cells
DiMilla, P. A., Quinn, J. A., Albelda, S. Μ., & Lauffenburger, D. A. (1992) · AIChE Journal · doi:10.1002/aic.690380712 · Cited by 70 · see citing works
Heyder, C., Gloria-Maercker, E., Entschladen, F., Hatzmann, W., Niggemann, B., nker, K. Z. X. E., & Dittmar, T. (2002) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-002-0377-7 · Cited by 59 · see citing works
Sahni, A., Arévalo, M. T., Sahni, S., & Simpson‐Haidaris, P. J. (2009) · International Journal of Cancer · doi:10.1002/ijc.24340 · Cited by 51 · see citing works
Permeability of single capillaries to intermediate-sized colored solutes
CURRY, F. E., Huxley, V. H., & Adamson, R. H. (1983) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1983.245.3.h495 · Cited by 50 · see citing works
Tumor-conditioned medium increases macromolecular permeability of endothelial cell monolayer
Utoguchi, N., Mizuguchi, H., Saeki, K., Ikeda, K., Tsutsumi, Y., Nakagawa, S., & Mayumi, T. (1995) · Cancer Letters · doi:10.1016/0304-3835(95)90151-5 · Cited by 24 · see citing works
Paracrine VEGF/VE-Cadherin Action on Ovarian Cancer Permeability
Hu, L., Ferrara, N., & Jaffe, R. B. (2006) · Experimental Biology and Medicine · doi:10.1177/153537020623101010 · Cited by 13 · see citing works
Systemic Analysis of Tumor Cell-Induced Endothelial Calcium Signaling and Junction Disassembly
Peng, H., & Dong, C. (2009) · Cellular and Molecular Bioengineering · doi:10.1007/s12195-009-0067-5 · Cited by 11 · see citing works
Flagged first, then by citations
Research works printed but not linked: 4
- [39]Zijlstra A Mellor R Panzarella G Aimes RT Hooper JD Marchenko ND Quigley JP Cancer Res 2002 62 7083 7092 12460930
- [50]Crissman JD Hatfield JS Menter DG Sloane B Honn KV Cancer Res 1988 48 4065 4072 3383198
- [51]Koop S Khokha R Schmidt EE MacDonald IC Morris VL Chambers AF Groom AC Cancer Res 1994 54 4791 4797 8062280
- [52]EJ Philadelphia W. B. Saunders 1928
Cited by
Sorted by citations
Bhatia, S. N., & Ingber, D. E. (2014) · Nature Biotechnology · doi:10.1038/nbt.2989 · Cited by 3,305 · see citing works
Modelling cancer in microfluidic human organs-on-chips
Sontheimer-Phelps, A., Hassell, B. A., & Ingber, D. E. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-018-0104-6 · Cited by 906 · see citing works
In Vitro Tumor Models: Advantages, Disadvantages, Variables, and Selecting the Right Platform
Katt, M. E., Placone, A. L., Wong, A. D., Xu, Z. S., & Searson, P. C. (2016) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2016.00012 · Cited by 754 · see citing works
Campisi, M., Shin, Y., Osaki, T., Hajal, C., Chiono, V., & Kamm, R. D. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.07.014 · Cited by 718 · see citing works
Self-citationOrgans-on-a-Chip: A Fast Track for Engineered Human Tissues in Drug Development
Ronaldson-Bouchard, K., & Vunjak-Novakovic, G. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.02.011 · Cited by 657 · see citing works
Engineered In Vitro Disease Models
Benam, K. H., Dauth, S., Hassell, B., Herland, A., Jain, A., Jang, K.-J., Karalis, K., Kim, H. J., MacQueen, L., Mahmoodian, R., et al. (2015) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012414-040418 · Cited by 554 · see citing works
Spiegel, A., Brooks, M. W., Houshyar, S., Reinhardt, F., Ardolino, M., Fessler, E., Chen, M. B., Krall, J. A., Cock, J. M. D., Zervantonakis, I. K., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-1157 · Cited by 480 · see citing works
Self-citationFluids and their mechanics in tumour transit: shaping metastasis
Follain, G., Herrmann, D., Harlepp, S., Hyenne, V., Osmani, N., Warren, S. C., Timpson, P., & Goetz, J. G. (2019) · Nature reviews. Cancer · doi:10.1038/s41568-019-0221-x · Cited by 413 · see citing works
Sleeboom, J. J. F., van Tienderen, G. S., Schenke‐Layland, K., van der Laan, L. J. W., Khalil, A. A., & Verstegen, M. M. A. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adg3840 · Cited by 391 · see citing works
Chen, M. B., Whisler, J. A., Fröse, J., Yu, C., Shin, Y., & Kamm, R. D. (2017) · Nature Protocols · doi:10.1038/nprot.2017.018 · Cited by 385 · see citing works
Self-citationOrgan-on-a chip systems: microengineering to biomimic living systems
Zheng, F., Fu, F., Cheng, Y., Wang, C., Zhao, Y., & Gu, Z. (2016) · Small · doi:10.1002/smll.201503208 · Cited by 338 · see citing works
Vascularized organoids on a chip: strategies for engineering organoids with functional vasculature
Zhang, S., Wan, Z., & Kamm, R. D. (2021) · Lab on a Chip · doi:10.1039/d0lc01186j · Cited by 317 · see citing works
Self-citationMicrofluidic techniques for development of 3D vascularized tissue
Hasan, A., Paul, A., Vrana, N. E., Zhao, X., Memic, A., Hwang, Y.-S., Dokmeci, M. R., & Khademhosseini, A. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.04.091 · Cited by 282 · see citing works
Penny, H. L., Sieow, J. L., Adriani, G., Yeap, W. H., See, P., Luis, B. S., Lee, B. T. K., Lee, T. K., Mak, S. Y., Ho, Y. S., et al. (2016) · OncoImmunology · doi:10.1080/2162402x.2016.1191731 · Cited by 255 · see citing works
Self-citationEnhanced substrate stress relaxation promotes filopodia-mediated cell migration
Adebowale, K., Gong, Z., Hou, J., Wisdom, K. M., Garbett, D., Lee, H.-P., Nam, S., Meyer, T., Odde, D. J., Shenoy, V. B., et al. (2021) · Nature Materials · doi:10.1038/s41563-021-00981-w · Cited by 247 · see citing works
Control of Perfusable Microvascular Network Morphology Using a Multiculture Microfluidic System
Whisler, J. A., Chen, M. B., & Kamm, R. D. (2012) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2013.0370 · Cited by 240 · see citing works
Self-citationJeon, J. S., Bersini, S., Whisler, J. A., Chen, M. B., Dubini, G., Charest, J. L., Moretti, M., & Kamm, R. D. (2014) · Integrative Biology · doi:10.1039/c3ib40267c · Cited by 229 · see citing works
Self-citationMicrofluidics: A New Tool for Modeling Cancer–Immune Interactions
Boussommier-Calleja, A., Li, R., Chen, M. B., Wong, S. C., & Kamm, R. D. (2016) · Trends in Cancer · doi:10.1016/j.trecan.2015.12.003 · Cited by 224 · see citing works
“In addition, μVNs replicate better the 3D vessel architecture and endothelial barrier function [21].”
BackgroundSelf-citationTumour-on-a-chip: microfluidic models of tumour morphology, growth and microenvironment
Tsai, H.-F., Trubelja, A., Shen, A. Q., & Bao, G. (2017) · Journal of The Royal Society Interface · doi:10.1098/rsif.2017.0137 · Cited by 214 · see citing works
Trujillo-de Santiago, G., Flores-Garza, B. G., Tavares-Negrete, J. A., Lara-Mayorga, I. M., González-Gamboa, I., Zhang, Y. S., Rojas-Martínez, A., Ortiz-López, R., & Álvarez, M. M. (2019) · Materials · doi:10.3390/ma12182945 · Cited by 184 · see citing works
“[48-53] [54-72] Spheroids in microfluidic chambers Spheroids in a hydrogel matrix”
Chen, M. B., Hajal, C., Benjamin, D. C., Yu, C., Azizgolshani, H., Hynes, R. O., & Kamm, R. D. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1715932115 · Cited by 183 · see citing works
Self-citationTraversing the basement membrane in vivo: A diversity of strategies
Kelley, L. C., Lohmer, L. L., Hagedorn, E. J., & Sherwood, D. R. (2014) · The Journal of Cell Biology · doi:10.1083/jcb.201311112 · Cited by 183 · see citing works
Parlato, S., De Ninno, A., Molfetta, R., Toschi, E., Salerno, D., Mencattini, A., Romagnoli, G., Fragale, A., Roccazzello, L., Buoncervello, M., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-01013-x · Cited by 181 · see citing works
Advances in On-Chip Vascularization
Haase, K., & Kamm, R. D. (2017) · Regenerative Medicine · doi:10.2217/rme-2016-0152 · Cited by 172 · see citing works
Self-citationThe effects of monocytes on tumor cell extravasation in a 3D vascularized microfluidic model
Boussommier-Calleja, A., Atiyas, Y., Haase, K., Headley, M., Lewis, C., & Kamm, R. D. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2018.03.005 · Cited by 158 · see citing works
Self-citationElucidation of the Roles of Tumor Integrin β1 in the Extravasation Stage of the Metastasis Cascade
Chen, M. B., Lamar, J. M., Li, R., Hynes, R. O., & Kamm, R. D. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-1325 · Cited by 158 · see citing works
Self-citationVasculature-On-A-Chip for In Vitro Disease Models
Kim, S., Kim, W., Lim, S., & Jeon, J. S. (2017) · Bioengineering · doi:10.3390/bioengineering4010008 · Cited by 158 · see citing works
Self-citationA review of microfluidic approaches for investigating cancer extravasation during metastasis
Ma, Y.-H. V., Middleton, K., You, L., & Sun, Y. (2018) · Microsystems & Nanoengineering · doi:10.1038/micronano.2017.104 · Cited by 154 · see citing works
The Mechanics of Single Cell and Collective Migration of Tumor Cells
Lintz, M., Muñoz, A., & Reinhart‐King, C. A. (2016) · Journal of Biomechanical Engineering · doi:10.1115/1.4035121 · Cited by 154 · see citing works
Shao, Y., & Fu, J. (2013) · Advanced Materials · doi:10.1002/adma.201304431 · Cited by 148 · see citing works
Álvarez, M. M., Aizenberg, J., Analoui, M., Andrews, A. M., Bisker, G., Boyden, E. S., Kamm, R. D., Karp, J. M., Mooney, D. J., Öklü, R., et al. (2017) · ACS Nano · doi:10.1021/acsnano.7b01493 · Cited by 137 · see citing works
Self-citationFabrication of 3D Biomimetic Microfluidic Networks in Hydrogels
Heintz, K. A., Bregenzer, M. E., Mantle, J. L., Lee, K. H., West, J. L., & Slater, J. H. (2016) · Advanced Healthcare Materials · doi:10.1002/adhm.201600351 · Cited by 135 · see citing works
Bioreactor technologies to support liver function in vitro
Ebrahimkhani, M. R., Neiman, J. A. S., Raredon, M. S. B., Hughes, D. J., & Griffith, L. G. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.02.011 · Cited by 134 · see citing works
Engineered models to parse apart the metastatic cascade
Hapach, L. A., Mosier, J. A., Wang, W., & Reinhart‐King, C. A. (2019) · npj Precision Oncology · doi:10.1038/s41698-019-0092-3 · Cited by 133 · see citing works
3D-printed fluidic networks as vasculature for engineered tissue
Kinstlinger, I. S., & Miller, J. S. (2016) · Lab on a Chip · doi:10.1039/c6lc00193a · Cited by 132 · see citing works
A microfluidic platform for quantitative analysis of cancer angiogenesis and intravasation
Lee, H., Park, W., Ryu, H., & Jeon, N. L. (2014) · Biomicrofluidics · doi:10.1063/1.4894595 · Cited by 130 · see citing works
Applications of tumor chip technology
Hachey, S. J., & Hughes, C. C. W. (2018) · Lab on a Chip · doi:10.1039/c8lc00330k · Cited by 128 · see citing works
A Chemomechanical Model for Nuclear Morphology and Stresses during Cell Transendothelial Migration
Cao, X., Moeendarbary, E., Isermann, P., Davidson, P. M., Wang, X., Chen, M. B., Burkart, A. K., Lammerding, J., Kamm, R. D., & Shenoy, V. B. (2016) · Biophysical Journal · doi:10.1016/j.bpj.2016.08.011 · Cited by 127 · see citing works
Self-citationMetastasis of circulating tumor cells: Favorable soil or suitable biomechanics, or both?
Azevedo, A. S., Follain, G., Patthabhiraman, S., Harlepp, S., & Goetz, J. G. (2015) · Cell Adhesion & Migration · doi:10.1080/19336918.2015.1059563 · Cited by 126 · see citing works
Sato, M., Sasaki, N., Ato, M., Hirakawa, S., Sato, K., & Sato, K. (2015) · PLOS ONE · doi:10.1371/journal.pone.0137301 · Cited by 124 · see citing works
Pisano, M., Triacca, V., Barbee, K. A., & Swartz, M. A. (2015) · Integrative Biology · doi:10.1039/c5ib00085h · Cited by 112 · see citing works
Engineering Breast Cancer Microenvironments and 3D Bioprinting
Belgodere, J. A., King, C. T., Bursavich, J. B., Burow, M. E., Martin, E. C., & Jung, J. P. (2018) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2018.00066 · Cited by 111 · see citing works
Wang, X., Sun, Q., & Pei, J. (2018) · Micromachines · doi:10.3390/mi9100493 · Cited by 106 · see citing works
Circulating Tumor Cells: When a Solid Tumor Meets a Fluid Microenvironment
Rejniak, K. A. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-42023-3_5 · Cited by 104 · see citing works
Ho, Y. T., Kamm, R. D., & Kah, J. C. Y. (2018) · Nanoscale · doi:10.1039/c8nr02393j · Cited by 102 · see citing works
Self-citationMak, M., Zaman, M. H., Kamm, R. D., & Kim, T. (2016) · Nature Communications · doi:10.1038/ncomms10323 · Cited by 102 · see citing works
Self-citationBlood Vessel Organoids for Development and Disease
Salewskij, K., & Penninger, J. M. (2023) · Circulation Research · doi:10.1161/circresaha.122.321768 · Cited by 100 · see citing works
Grafting of 3D Bioprinting to In Vitro Drug Screening: A Review
Nie, J., Gao, Q., Fu, J., & He, Y. (2020) · Advanced Healthcare Materials · doi:10.1002/adhm.201901773 · Cited by 99 · see citing works
Single-Cell Migration in Complex Microenvironments: Mechanics and Signaling Dynamics
Mak, M., Spill, F., Kamm, R. D., & Zaman, M. H. (2015) · Journal of Biomechanical Engineering · doi:10.1115/1.4032188 · Cited by 93 · see citing works
Self-citationMicrofluidic-based vascularized microphysiological systems
Lee, S., Ko, J., Park, D., Lee, B., Chung, M., Lee, Y., & Jeon, N. L. (2018) · Lab on a Chip · doi:10.1039/c8lc00285a · Cited by 92 · see citing works
Peela, N., Truong, D. D., Saini, H., Chu, H., Mashaghi, S., Ham, S. L., Singh, S. K., Tavana, H., Mosadegh, B., & Nikkhah, M. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.04.017 · Cited by 91 · see citing works
Microfluidic platform for studying osteocyte mechanoregulation of breast cancer bone metastasis
Mei, X., Middleton, K., Shim, D., Wan, Q., Xu, L., Ma, Y.-H. V., Devadas, D., Walji, N., Wang, L., Young, E. W. K., et al. (2019) · Integrative Biology · doi:10.1093/intbio/zyz008 · Cited by 88 · see citing works
Song, J., Miermont, A., Lim, C. T., & Kamm, R. D. (2018) · Scientific Reports · doi:10.1038/s41598-018-36381-5 · Cited by 87 · see citing works
Self-citationZibara, K., Awada, Z., Dib, L., Saghir, J. E., Al-Ghadban, S. I., Ibrik, A., Zein, N. E., & El-Sabban, M. E. (2015) · Scientific Reports · doi:10.1038/srep12598 · Cited by 87 · see citing works
Offeddu, G. S., Hajal, C., Foley, C., Wan, Z., Ibrahim, L. I., Coughlin, M. F., & Kamm, R. D. (2021) · Communications Biology · doi:10.1038/s42003-021-01774-2 · Cited by 87 · see citing works
Self-citationStudying the influence of angiogenesis in in vitro cancer model systems
Roudsari, L. C., & West, J. L. (2015) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.11.004 · Cited by 86 · see citing works
Lim, J., Ching, H., Yoon, J., Jeon, N. L., & Kim, Y. (2021) · Nano Convergence · doi:10.1186/s40580-021-00261-y · Cited by 83 · see citing works
A gelatin hydrogel to study endometrial angiogenesis and trophoblast invasion
Zambuto, S. G., Clancy, K. B. H., & Harley, B. A. C. (2019) · Interface Focus · doi:10.1098/rsfs.2019.0016 · Cited by 82 · see citing works
Hynes, W. F., Pepona, M., Robertson, C., Alvarado, J. A., Dubbin, K., Triplett, M., Adorno, J. J., Randles, A. P., & Moya, M. L. (2020) · Science Advances · doi:10.1126/sciadv.abb3308 · Cited by 82 · see citing works
“Open-top” microfluidic device for in vitro three-dimensional capillary beds
Oh, S., Ryu, H., Tahk, D., Ko, J., Chung, Y., Lee, H., Lee, T. R., & Jeon, N. L. (2017) · Lab on a Chip · doi:10.1039/c7lc00646b · Cited by 82 · see citing works
Epithelial-Mesenchymal Transition Induces Podocalyxin to Promote Extravasation via Ezrin Signaling
Fröse, J., Chen, M. B., Hebron, K. E., Reinhardt, F., Hajal, C., Zijlstra, A., Kamm, R. D., & Weinberg, R. A. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.06.092 · Cited by 79 · see citing works
Self-citationMicrofluidic lumen-based systems for advancing tubular organ modeling
Virumbrales-Muñoz, M., Ayuso, J. M., Gong, M. M., Humayun, M., Livingston, M. K., Lugo-Cintrón, K. M., McMinn, P. H., Álvarez-García, Y. R., & Beebe, D. J. (2020) · Chemical Society Reviews · doi:10.1039/d0cs00705f · Cited by 77 · see citing works
Modeling Endothelialized Hepatic Tumor Microtissues for Drug Screening
Wang, Y., Kankala, R. K., Zhang, J., Hao, L., Zhu, K., Wang, S., Zhang, Y. S., & Chen, A. (2020) · Advanced Science · doi:10.1002/advs.202002002 · Cited by 74 · see citing works
Teo, G. S. L., Yang, Z., Carman, C. V., Karp, J. M., & Lin, C. P. (2014) · Stem Cells · doi:10.1002/stem.1848 · Cited by 73 · see citing works
Ozkan, A., Ghousifam, N., Hoopes, P. J., Yankeelov, T. E., & Rylander, M. N. (2019) · Biotechnology and Bioengineering · doi:10.1002/bit.26919 · Cited by 73 · see citing works
Quantification of cancer cell extravasation in vivo
Kim, Y., Williams, K. C., Gavin, C. T., Jardine, E., Chambers, A. F., & Leong, H. S. (2016) · Nature Protocols · doi:10.1038/nprot.2016.050 · Cited by 72 · see citing works
In vitro models of the metastatic cascade: from local invasion to extravasation
Bersini, S., Jeon, J. S., Moretti, M., & Kamm, R. D. (2014) · Drug Discovery Today · doi:10.1016/j.drudis.2013.12.006 · Cited by 71 · see citing works
Self-citationMechanical stress driven by rigidity sensing governs epithelial stability
Sonam, S., Balasubramaniam, L., Lin, S., Yow, I., Pi-Jaumà, I., Jebane, C., Karnat, M., Toyama, Y., Marcq, P., Prost, J., et al. (2022) · Nature Physics · doi:10.1038/s41567-022-01826-2 · Cited by 71 · see citing works
Stadler, M., Walter, S., Walzl, A., Kramer, N., Unger, C., Scherzer, M., Unterleuthner, D., Hengstschläger, M., Krupitza, G., & Dolznig, H. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.08.007 · Cited by 70 · see citing works
Emerging tumor-on-chips with electrochemical biosensors
Lei, L., Ma, B., Xu, C., & Liu, H. (2022) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2022.116640 · Cited by 69 · see citing works
Hajal, C., Ibrahim, L., Serrano, J. C., Offeddu, G. S., & Kamm, R. D. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2020.120470 · Cited by 68 · see citing works
Self-citationPozzi, S., Scomparin, A., Dangoor, S. I., Ajamil, D. R., Ofek, P., Neufeld, L., Krivitsky, A., Vaskovich‐Koubi, D., Kleiner, R., Dey, P., et al. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.04.001 · Cited by 68 · see citing works
Kumar, V., & Varghese, S. (2018) · Advanced Healthcare Materials · doi:10.1002/adhm.201801198 · Cited by 68 · see citing works
Microfluidic models for adoptive cell-mediated cancer immunotherapies
Adriani, G., Pavesi, A., Tan, A. T., Bertoletti, A., Thiery, J. P., & Kamm, R. D. (2016) · Drug Discovery Today · doi:10.1016/j.drudis.2016.05.006 · Cited by 67 · see citing works
Self-citationCancer-on-chip models for metastasis: importance of the tumor microenvironment
Jouybar, M., de Winde, C. M., Wolf, K., Friedl, P., Mebius, R. E., & den Toonder, J. M. J. (2024) · Trends in Biotechnology · doi:10.1016/j.tibtech.2023.10.001 · Cited by 66 · see citing works
Fluid mechanics in circulating tumour cells: Role in metastasis and treatment strategies
Rajput, S., Sharma, P. K., & Malviya, R. (2023) · Medicine in Drug Discovery · doi:10.1016/j.medidd.2023.100158 · Cited by 66 · see citing works
Biomaterials to model and measure epithelial cancers
Beri, P., Matte, B. F., Fattet, L., Kim, D., Yang, J., & Engler, A. J. (2018) · Nature Reviews Materials · doi:10.1038/s41578-018-0051-6 · Cited by 66 · see citing works
Ngo, M. T., & Harley, B. A. C. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201700687 · Cited by 64 · see citing works
A Robust Method for Perfusable Microvascular Network Formation In Vitro
Wan, Z., Zhong, A. X., Zhang, S., Pavlou, G., Coughlin, M. F., Shelton, S. E., Nguyen, H. T., Lorch, J. H., Barbie, D. A., & Kamm, R. D. (2022) · Small Methods · doi:10.1002/smtd.202200143 · Cited by 63 · see citing works
Self-citationPlatelet cancer cell interplay as a new therapeutic target
Morris, K., Schnoor, B., & Papa, A. (2022) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2022.188770 · Cited by 63 · see citing works
Three-dimensional cage-like microscaffolds for cell invasion studies
Spagnolo, B., Brunetti, V., Leménager, G., Luca, E. D., Sileo, L., Pellegrino, T., Pompa, P. P., Vittorio, M. D., & Pisanello, F. (2015) · Scientific Reports · doi:10.1038/srep10531 · Cited by 63 · see citing works
The Cancer Microenvironment: Mechanical Challenges of the Metastatic Cascade
Amos, S. E., & Choi, Y. S. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.625859 · Cited by 62 · see citing works
Ngo, M. T., & Harley, B. A. C. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.06.013 · Cited by 62 · see citing works
Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology
Pradhan, S., Banda, O. A., Farino, C. J., Sperduto, J. L., Keller, K. A., Taitano, R. A., & Slater, J. H. (2020) · Advanced Healthcare Materials · doi:10.1002/adhm.201901255 · Cited by 61 · see citing works
The Use of Microfluidic Platforms to Probe the Mechanism of Cancer Cell Extravasation
Coughlin, M. F., & Kamm, R. D. (2020) · Advanced Healthcare Materials · doi:10.1002/adhm.201901410 · Cited by 59 · see citing works
Self-citationIn vitro 3D Systems to Model Tumor Angiogenesis and Interactions With Stromal Cells
Brassard-Jollive, N., Monnot, C., Muller, L., & Germain, S. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.594903 · Cited by 58 · see citing works
A microchip platform for interrogating tumor–macrophage paracrine signaling at the single-cell level
Elitaş, M., Brower, K. K., Lu, Y., Chen, J. J. F., & Fan, R. (2014) · Lab on a Chip · doi:10.1039/c4lc00676c · Cited by 57 · see citing works
Oliver, C. R., Altemus, M., Westerhof, T. M., Cheriyan, H., Cheng, X., Dziubinski, M., Wu, Z., Yates, J. A., Morikawa, A., Heth, J., et al. (2019) · Lab on a Chip · doi:10.1039/c8lc01387j · Cited by 56 · see citing works
Reality Check for Nanomaterial‐Mediated Therapy with 3D Biomimetic Culture Systems
Tay, C. Y., Muthu, M. S., Chia, S. L., Nguyen, K. T., Feng, S., & Leong, D. T. (2016) · Advanced Functional Materials · doi:10.1002/adfm.201600476 · Cited by 54 · see citing works
Offeddu, G. S., Possenti, L., Loessberg-Zahl, J., Zunino, P., Roberts, J., Han, X., Hickman, D., Knutson, C. G., & Kamm, R. D. (2019) · Small · doi:10.1002/smll.201902393 · Cited by 54 · see citing works
Self-citationHolenstein, C. N., Horvath, A. N., Schär, B., Schoenenberger, A. D., Bollhalder, M., Goedecke, N., Bartalena, G., Otto, O., Herbig, M., Guck, J. R., et al. (2019) · Molecular Biology of the Cell · doi:10.1091/mbc.e18-08-0545 · Cited by 53 · see citing works
Mondadori, C., Crippa, M., Moretti, M., Candrian, C., Lopa, S., & Arrigoni, C. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00907 · Cited by 50 · see citing works
Visualizing cancer extravasation: from mechanistic studies to drug development
Cheng, X., & Cheng, K. (2020) · Cancer and Metastasis Reviews · doi:10.1007/s10555-020-09942-2 · Cited by 50 · see citing works
Microfabrication and microfluidics for muscle tissue models
Uzel, S. G. M., Pavesi, A., & Kamm, R. D. (2014) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2014.08.013 · Cited by 50 · see citing works
Self-citationStrobel, H. A., Moss, S. M., & Hoying, J. B. (2023) · Bioengineering · doi:10.3390/bioengineering10020124 · Cited by 49 · see citing works
Cancer-on-a-chip for precision cancer medicine
Liu, L., Wang, H., Chen, R., Song, Y., Wei, W., Baek, D. S. H., Gillin, M., Kurabayashi, K., & Chen, W. (2025) · Lab on a Chip · doi:10.1039/d4lc01043d · Cited by 47 · see citing works
Meier, C., Spitschak, A., Abshagen, K., Gupta, S. K., Mor, J. M., Olaf Wolkenhauer, A., Haier, J., Vollmar, B., Alla, V., & Pützer, B. M. (2014) · The Journal of Pathology · doi:10.1002/path.4400 · Cited by 47 · see citing works
Nanomechanics in Monitoring the Effectiveness of Drugs Targeting the Cancer Cell Cytoskeleton
Kubiak, A., Zieliński, T., Pabijan, J., & Lekka, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228786 · Cited by 47 · see citing works
Riehl, B. D., Kim, E., Bouzid, T., & Lim, J. Y. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.608526 · Cited by 47 · see citing works
Vascularization of engineered organoids
Liu, H., Zhang, X., Liu, J., & Qin, J. (2023) · BMEMat · doi:10.1002/bmm2.12031 · Cited by 46 · see citing works
- Authors
- Chen, M. B., Whisler, J. A., Jeon, J. S., & Kamm, R. D.
- Affiliations
- Massachusetts Institute of Technology (US)
- Corresponding author
- Kamm, Roger D.
- Venue
- Integrative Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013
- Volume
- 5
- Issue
- 10
- Pages
- 1262
- ISSN
- 1757-9694 (ISSN-L)
- 1757-9708
- PMC
- PMC4038741
- OpenAlex
- W1858855509
- Cited by
- 308
- References
- 53
- Citations by year
- 2026: 16 · 2025: 19 · 2024: 20 · 2023: 21 · 2022: 28 · 2021: 28 · 2020: 29 · 2019: 29 · 2018: 32 · 2017: 17 · 2016: 29 · 2015: 18 · 2014: 17 · 2013: 4 · 2012: 1
- FWCI
- 12.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Integrative Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- PMC
- Funders
- National Science Foundation
- Emergent Behaviors of Integrated Cellular Systems
- National Cancer Institute (R33CA174550)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- tumor cell extravasation, metastasis, endothelial barrier function, endothelial junctions, basement membrane deposition, vascular permeability, inflammatory cytokines, vasculogenesis, transendothelial migration, MDA-MB-231 cells, MCF10A cells, cell clusters, time-lapse microscopy
- MeSH terms
- Breast Neoplasms, Capillary Permeability, Cell Communication, Equipment Design, Humans, Intercellular Junctions, Neovascularization, Pathologic, Equipment Failure Analysis, Cell Line, Tumor, Microfluidic Analytical Techniques, Microvessels
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
