CoChat
Sign Up
Cited by 1303D Printing in Biomedical ResearchMicrofluidic and Capillary Electrophoresis ApplicationsAngiogenesis and VEGF in Cancer

A microfluidic platform for quantitative analysis of cancer angiogenesis and intravasation

Open access
Lee, Hyunjae, Park, Woohyun, Ryu, Hyunryul, Jeon, Noo Li·2014·Biomicrofluidics
DOI 10.1063/1.4894595PMC PMC4189585
Open this paper in CoChat — free accountOpen PDF

Abstract

Understanding the mechanism behind cancer metastasis is a major challenge in cancer biology. Several in vitro models have been developed to mimic a cancer microenvironment by engineering cancer–endothelial cell (EC) and cancer-stromal cell interactions. It has been challenging to realistically mimic angiogenesis, intravasation, and extravasation using macro-scale approaches but recent progress in microfluidics technology has begun to yield promising results. We present a metastasis chip that produce microvessels, where EC and stromal cells can be patterned in close proximity to tumor cells. The vessels are formed following a natural morphogenic process and have smooth boundaries with proper cell-cell junctions. The engineered microvessels are perfusable and have well-defined openings toward inlet and outlet channels. The ability to introduce cancer cells into different locations bordering to the microvessel wall allowed generation and maintenance of appropriate spatial gradients of growth factors and attractants. Cancer angiogenesis and its inhibition by anti-vascular endothelial growth factor (bevacizumab) treatment were successfully reproduced in the metastasis chip. Cancer intravasation and its modulation by treatment of tumor necrosis factor-α were also modeled. Compared to other models, the unique design of the metastasis chip that engineers a clear EC-cancer interface allows precise imaging and quantification of angiogenic response as well as tumor cell trans-endothelial migration. The metastasis chip presented here has potential applications in the investigation of fundamental cancer biology as well as in drug screening.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1063/1.4894595

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.

A few free checks a day · papers already verified open instantly · results are public

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?

  • Microfluidic assays have been designed to replicate aspects of several metastatic steps, including EMT, cancer cell invasion and adhesion, and intra- and extravasation.

    “Microfluidic assays have been designed to replicate certain aspects of several of these steps, such as EMT[13, 14], cancer cell invasion and adhesion[15–17], and intra-[18, 19] and extravasation[17, 20– 22] (see Text Box 3).”

    From Microfluidics: A New Tool for Modeling Cancer–Immune Interactions (2016) · cites this paper as [19]

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 36 · Cited by 130

Research works printed but not linked: 34

  1. [1]1. G. Bergers and L. E. Benjamin, Nat. Rev. Cancer 3(6), 401-410 (2003).
  2. [2]2. P. Carmeliet and R. K. Jain, Nature 407(6801), 249-257 (2000).
  3. [3]3. E. Sahai, Nat. Rev. Cancer 7(10), 737-749 (2007).
  4. [4]4. M. Tsujii, S. Kawano, S. Tsuji, H. Sawaoka, M. Hori, and R. N. DuBois, Cell 93(5), 705-716 (1998).
  5. [5]5. A. Abdollahi, D. W. Griggs, H. Zieher, A. Roth, K. E. Lipson, R. Saffrich, H.-J. Gr€ one, D. E. Hallahan, R. A. Reisfeld, and J. Debus, Clin. Cancer Res. 11(17), 6270-6279 (2005).
  6. [6]6. T. Kusama, M. Mukai, M. Tatsuta, H. Nakamura, and M. Inoue, Int. J. Oncol. 29(1), 217-223 (2006).
  7. [7]7. T.-H. Lee, H. K. Avraham, S. Jiang, and S. Avraham, J. Biol. Chem. 278(7), 5277-5284 (2003).
  8. [8]8. F. Jin, U. Brockmeier, F. Otterbach, and E. Metzen, Mol. Cancer Res. 10(8), 1021-1031 (2012).
  9. [9]9. R. H. Kramer and G. L. Nicolson, Proc. Natl. Acad. Sci. U.S.A. 76(11), 5704-5708 (1979).
  10. [10]10. A. Roetger, A. Merschjann, T. Dittmar, C. Jackisch, A. Barnekow, and B. Brandt, Am. J. Pathol. 153(6), 1797-1806 (1998).
  11. [11]11. B. A. Zabel, S. Lew en, R. D. Berahovich, J. C. Ja en, and T. J. Schall, Mol. Cancer 10, 73 (2011).
  12. [12]12. S. Chung, R. Sudo, V. Vickerman, I. K. Zervantonakis, and R. D. Kamm, Ann. Biomed. Eng. 38(3), 1164-1177 (2010).
  13. [13]13. H. Lee, M. Chung, and N. L. Jeon, MRS Bull. 39(01), 51-59 (2014).
  14. [14]14. S. Kim, H. Lee, M. Chung, and N. L. Jeon, Lab Chip 13(8), 1489-1500 (2013).
  15. [15]15. I. K. Zervantonakis, S. K. Hughes-Alford, J. L. Charest, J. S. Condeelis, F. B. Gertler, and R. D. Kamm, Proc. Natl. Acad. Sci. U.S.A. 109(34), 13515-13520 (2012).
  16. [16]16. J. S. Jeon, I. K. Zervantonakis, S. Chung, R. D. Kamm, and J. L. Charest, PloS One 8(2), e56910 (2013).
  17. [17]17. M. B. Chen, J. A. Whisler, J. S. Jeon, and R. D. Kamm, Integr. Biol. 5(10), 1262-1271 (2013).
  18. [19]19. J. H. Yeon, H. R. Ryu, M. Chung, Q. P. Hu, and N. L. Jeon, Lab Chip 12(16), 2815-2822 (2012).
  19. [20]20. C. P. Huang, J. Lu, H. Seon, A. P. Lee, L. A. Flanagan, H.-Y. Kim, A. J. Putnam, and N. L. Jeon, Lab Chip 9(12), 1740-1748 (2009).
  20. [21]21. J. Flament, F. Geffroy, C. Medina, C. Robic, J. F. Mayer, S. M eriaux, J. Valette, P. Robert, M. Port, and D. Le Bihan, Magn. Reson. Med. 69(1), 179-187 (2013).
  21. [22]22. F. Yuan, Y. Chen, M. Dellian, N. Safabakhsh, N. Ferrara, and R. K. Jain, Proc. Natl. Acad. Sci. U.S.A. 93(25), 14765-14770 (1996).
  22. [23]23. M. H. Wu, E. Ustinova, and H. J. Granger, J. Physiol. 532(3), 785-791 (2001).
  23. [24]24. P. W. Kazakoff, T. R. McGuire, E. B. Hoie, M. Cano, and P. L. Iversen, In Vitro Cell. Dev. Biol. Anim. 31(11), 846-852 (1995).
  24. [25]25. Y. Zheng, J. Chen, M. Craven, N. W. Choi, S. Totorica, A. Diaz-Santana, P. Kermani, B. Hempstead, C. Fischbach- Teschl, and J. A. L opez, Proc. Natl. Acad. Sci. U.S.A. 109(24), 9342-9347 (2012).
  25. [26]26. K. R. Pechman, D. L. Donohoe, D. P. Bedekar, S. N. Kurpad, R. G. Hoffmann, and K. M. Schmainda, J. Neuro-Oncol. 105(2), 233-239 (2011).
  26. [27]27. Q. D. Wu, J. H. Wang, C. Condron, D. Bouchier-Hayes, and H. P. Redmond, Am. J. Physiol. Cell Physiol. 280(4), C814-C822 (2001).
  27. [28]28. K. Zen, D.-Q. Liu, Y.-L. Guo, C. Wang, J. Shan, M. Fang, C.-Y. Zhang, and Y. Liu, PloS One 3(3), e1826 (2008).
  28. [29]29. J. Brett, H. Gerlach, P. Nawroth, S. Steinberg, G. Godman, and D. Stern, J. Exp. Med. 169(6), 1977-1991 (1989).
  29. [30]30. C. J. Horvath, T. J. Ferro, G. Jesmok, and A. B. Malik, Proc. Natl. Acad. Sci. U.S.A. 85(23), 9219-9223 (1988).
  30. [31]31. A. Burke-Gaffeyy and A. K. Keenan, Immunopharmacology 25(1), 1-9 (1993).
  31. [32]32. M. Liang, P. Zhang, and J. Fu, Cancer Lett. 258(1), 31-37 (2007).
  32. [33]33. K. J€ ohrer, K. Janke, J. Krugmann, M. Fiegl, and R. Greil, Clin. Cancer Res. 10(6), 1901-1910 (2004).
  33. [34]34. L. L. Bischel, E. W. Young, B. R. Mader, and D. J. Beebe, Biomaterials 34(5), 1471-1477 (2013).
  34. [35]35. Y.-H. Li and C. Zhu, Clin. Exp. Metastasis 17(5), 423-429 (1999).

Authors
Lee, H., Park, W., Ryu, H., & Jeon, N. L.
Affiliations
Seoul National University (KR)
ORCID
Venue
Biomicrofluidics
Publisher
AIP Publishing
Published
2014-09-01
Volume
8
Issue
5
Pages
054102-054102
ISSN
1932-1058 (ISSN-L)
DOI
10.1063/1.4894595
PMC
PMC4189585
OpenAlex
W2002785815
Cited by
130
References
36
Citations by year
2026: 6 · 2025: 6 · 2024: 10 · 2023: 13 · 2022: 9 · 2021: 16 · 2020: 8 · 2019: 17 · 2018: 19 · 2017: 10 · 2016: 11 · 2015: 4 · 2014: 1
FWCI
4.50
Type
journal article
Language
en
Open access
Locations
  • Biomicrofluidics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Brain Korea 21 Plus Project (2014-003894)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
  • Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords
tumor angiogenesis, microfluidics, tumor microenvironment, endothelial cells, stromal cells, bevacizumab, TNF-α, vascular endothelial growth factor, drug screening, metastasis

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