The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Lymphatic endothelium stimulates melanoma metastasis and invasion via MMP14-dependent Notch3 and β1-integrin activation
Abstract
Lymphatic invasion and lymph node metastasis correlate with poor clinical outcome in melanoma. However, the mechanisms of lymphatic dissemination in distant metastasis remain incompletely understood. We show here that exposure of expansively growing human WM852 melanoma cells, but not singly invasive Bowes cells, to lymphatic endothelial cells (LEC) in 3D co-culture facilitates melanoma distant organ metastasis in mice. To dissect the underlying molecular mechanisms, we established LEC co-cultures with different melanoma cells originating from primary tumors or metastases. Notably, the expansively growing metastatic melanoma cells adopted an invasively sprouting phenotype in 3D matrix that was dependent on MMP14, Notch3 and β1-integrin. Unexpectedly, MMP14 was necessary for LEC-induced Notch3 induction and coincident β1-integrin activation. Moreover, MMP14 and Notch3 were required for LEC-mediated metastasis of zebrafish xenografts. This study uncovers a unique mechanism whereby LEC contact promotes melanoma metastasis by inducing a reversible switch from 3D growth to invasively sprouting cell phenotype.
Overview
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
Verification
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?
MT1-MMP is highly expressed in various types of cancer cells and promotes cancer metastasis and angiogenesis.
“It is well documented that MT1-MMP is highly expressed in various types of cancer cells and promotes cancer metastasis and angiogenesis16,44,47–50.”
From Membrane type 1 matrix metalloproteinase promotes LDL receptor shedding and accelerates the development of atherosclerosis (2021) · cites this paper as [49]
The Results section reports that MMP14 (MT1-MMP) is frequently induced in invasive melanoma and that high expression correlates with melanoma progression and metastasis. The Discussion links MMP14 to invasive behavior but cautions that high MMP14 alone was not sufficient for distant metastasis. The paper does not establish high expression across various cancer types or show that MMP14 promotes angiogenesis; the angiogenesis passages concern other mechanisms or an assay adapted for this study. Page numbers are unavailable in our copy. (LLM, conf=0.88)
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.
Citations
Cites
Transparent Adult Zebrafish as a Tool for In Vivo Transplantation Analysis
White, R. M., Sessa, A., Burke, C., Bowman, T., LeBlanc, J., Ceol, C., Bourque, C., Dovey, M., Goessling, W., Burns, C. E., et al. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2007.11.002 · Cited by 1,408
Flagged first, then by citations
Research works printed but not linked: 41
- Alitalo, 2012, Interaction of tumor cells and lymphatic vessels in cancer progression, Oncogene, 31, 4499, 10.1038/onc.2011.602 · DOI
- Brütsch, 2010, Integrin cytoplasmic domain-associated protein-1 attenuates sprouting angiogenesis, Circulation Research, 107, 592, 10.1161/CIRCRESAHA.110.217257 · DOI
- Cabioglu, 2005, CCR7 and CXCR4 as novel biomarkers predicting axillary lymph node metastasis in T1 breast cancer, Clinical Cancer Research, 11, 5686, 10.1158/1078-0432.CCR-05-0014 · DOI
- Cao, 2008, Membrane type 1 matrix metalloproteinase induces epithelial-to-mesenchymal transition in prostate cancer, Journal of Biological Chemistry, 283, 6232, 10.1074/jbc.M705759200 · DOI
- Chapman, 2014, Heterogeneous tumor subpopulations cooperate to drive invasion, Cell Reports, 8, 688, 10.1016/j.celrep.2014.06.045 · DOI
- Cheng, 2011, KSHV-initiated notch activation leads to membrane-type-1 matrix metalloproteinase-dependent lymphatic endothelial-to-mesenchymal transition, Cell Host & Microbe, 10, 577, 10.1016/j.chom.2011.10.011 · DOI
- Danen, 1994, Emergence of alpha 5 beta 1 fibronectin- and alpha v beta 3 vitronectin-receptor expression in melanocytic tumour progression, Histopathology, 24, 249, 10.1111/j.1365-2559.1994.tb00517.x · DOI
- Das, 2013, Tumor cell entry into the lymph node is controlled by CCL1 chemokine expressed by lymph node lymphatic sinuses, The Journal of Experimental Medicine, 210, 1509, 10.1084/jem.20111627 · DOI
- Funahashi, 2011, Notch modulates VEGF action in endothelial cells by inducing Matrix Metalloprotease activity, Vascular Cell, 3, 2, 10.1186/2045-824X-3-2 · DOI
- Hofmann, 2000, Matrix metalloproteinases in human melanoma, Journal of Investigative Dermatology, 115, 337, 10.1046/j.1523-1747.2000.00068.x · DOI
- Howard, 2013, Notch signaling mediates melanoma-endothelial cell communication and melanoma cell migration, Pigment Cell & Melanoma Research, 26, 697, 10.1111/pcmr.12131 · DOI
- Kankaanpää, 2012, BioImageXD: an open, general-purpose and high-throughput image-processing platform, Nature Methods, 9, 683, 10.1038/nmeth.2047 · DOI
- Kato, 2012, The primacy of β1 integrin activation in the metastatic cascade, PLoS One, 7, e46576, 10.1371/journal.pone.0046576 · DOI
- Kerjaschki, 2011, Lipoxygenase mediates invasion of intrametastatic lymphatic vessels and propagates lymph node metastasis of human mammary carcinoma xenografts in mouse, Journal of Clinical Investigation, 121, 2000, 10.1172/JCI44751 · DOI
- Korff, 1998, Integration of endothelial cells in multicellular spheroids prevents apoptosis and induces differentiation, The Journal of Cell Biology, 143, 1341, 10.1083/jcb.143.5.1341 · DOI
- Lambert, 2017, Emerging biological principles of metastasis, Cell, 168, 670, 10.1016/j.cell.2016.11.037 · DOI
- Liu, 2011, Re-expression of AKAP12 inhibits progression and metastasis potential of colorectal carcinoma in vivo and in vitro, PLoS One, 6, e24015, 10.1371/journal.pone.0024015 · DOI
- Liu, 2014, Notch3 is important for TGF-β-induced epithelial-mesenchymal transition in non-small cell lung cancer bone metastasis by regulating ZEB-1, Cancer Gene Therapy, 21, 364, 10.1038/cgt.2014.39 · DOI
- Love, 2014, Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2, Genome Biology, 15, 550, 10.1186/s13059-014-0550-8 · DOI · Paper page
- Ma, 2014, Atractylenolide I-mediated Notch pathway inhibition attenuates gastric cancer stem cell traits, Biochemical and Biophysical Research Communications, 450, 353, 10.1016/j.bbrc.2014.05.110 · DOI
- Meier, 2002, Metastatic pathways and time courses in the orderly progression of cutaneous melanoma, British Journal of Dermatology, 147, 62, 10.1046/j.1365-2133.2002.04867.x · DOI
- Mori, 2013, Transmembrane/cytoplasmic, rather than catalytic, domains of Mmp14 signal to MAPK activation and mammary branching morphogenesis via binding to integrin β1, Development, 140, 343, 10.1242/dev.084236 · DOI · Paper page
- Moro, 2014, Metalloproteinases in melanoma, European Journal of Cell Biology, 93, 23, 10.1016/j.ejcb.2014.01.002 · DOI
- Natali, 1993, Integrin expression in cutaneous malignant melanoma: association of the alpha 3/beta 1 heterodimer with tumor progression, International Journal of Cancer, 54, 68, 10.1002/ijc.2910540112 · DOI
- Niakosari, 2008, Lymphatic invasion identified by monoclonal antibody D2-40, younger age, and ulceration: predictors of sentinel lymph node involvement in primary cutaneous melanoma, Archives of Dermatology, 144, 462, 10.1001/archderm.144.4.462 · DOI
- Nuesslein-Volhard, 2011, Zebrafish: A Practical Approach
- Paatero, 2018, Zebrafish embryo xenograft and metastasis assay, Bio-Protocol, 8, 10.21769/BioProtoc.3027 · DOI
- Piskounova, 2015, Oxidative stress inhibits distant metastasis by human melanoma cells, Nature, 527, 186, 10.1038/nature15726 · DOI · Paper page
- Schindelin, 2012, Fiji: an open-source platform for biological-image analysis, Nature Methods, 9, 676, 10.1038/nmeth.2019 · DOI · Paper page
- Shields, 2007, Autologous chemotaxis as a mechanism of tumor cell homing to lymphatics via interstitial flow and autocrine CCR7 signaling, Cancer Cell, 11, 526, 10.1016/j.ccr.2007.04.020 · DOI
- Stine, 2011, Integration of genotypic and phenotypic screening reveals molecular mediators of melanoma-stromal interaction, Cancer Research, 71, 2433, 10.1158/0008-5472.CAN-10-1875 · DOI
- Strilic, 2017, Intravascular survival and extravasation of tumor cells, Cancer Cell, 32, 282, 10.1016/j.ccell.2017.07.001 · DOI
- Tang, 2013, MT1-MMP-dependent control of skeletal stem cell commitment via a β1-integrin/YAP/TAZ signaling axis, Developmental Cell, 25, 402, 10.1016/j.devcel.2013.04.011 · DOI
- Tatti, 2011, Membrane-type-3 matrix metalloproteinase (MT3-MMP) functions as a matrix composition-dependent effector of melanoma cell invasion, PLoS One, 6, e28325, 10.1371/journal.pone.0028325 · DOI
- Tatti, 2015, MMP16 mediates a proteolytic switch to promote cell-cell adhesion, collagen alignment, and lymphatic invasion in melanoma, Cancer Research, 75, 2083, 10.1158/0008-5472.CAN-14-1923 · DOI
- Turunen, 2017, Membrane-type matrix metalloproteases as diverse effectors of cancer progression, Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1864, 1974, 10.1016/j.bbamcr.2017.04.002 · DOI
- Vandamme, 2014, Melanoma cells revive an embryonic transcriptional network to dictate phenotypic heterogeneity, Frontiers in Oncology, 4, 352, 10.3389/fonc.2014.00352 · DOI
- Villanueva, 2008, Melanoma and the tumor microenvironment, Current Oncology Reports, 10, 439, 10.1007/s11912-008-0067-y · DOI
- Vuoriluoto, 2011, Vimentin regulates EMT induction by Slug and oncogenic H-Ras and migration by governing Axl expression in breast cancer, Oncogene, 30, 1436, 10.1038/onc.2010.509 · DOI
- Westerfield, 2009, Essential Zebrafish Methods Cell and Developmental Biology
- Woskowicz, 2013, MT-LOOP-dependent localization of membrane type I matrix metalloproteinase (MT1-MMP) to the cell adhesion complexes promotes cancer cell invasion, Journal of Biological Chemistry, 288, 35126, 10.1074/jbc.M113.496067 · DOI
Cited by
Sorted by citations
MMP14 in sarcoma: a regulator of tumor microenvironment communication in connective tissues
Gonzalez-Molina, J., Gramolelli, S., Liao, Z., Carlson, J. W., Ojala, P. M., & Lehti, K. (2019) · Cells · doi:10.3390/cells8090991 · Cited by 89
Self-citationAlabi, A., Xia, X.-D., Gu, H.-M., Wang, F., Deng, S.-J., Yang, N., Adijiang, A., Douglas, D. N., Kneteman, N. M., Xue, Y., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22167-3 · Cited by 63
Metadata
- Authors
- Pekkonen, P., Alve, S., Balistreri, G., Gramolelli, S., Tatti-Bugaeva, O., Paatero, I., Niiranen, O., Tuohinto, K., Perälä, N., Taiwo, A., Zinovkina, N., Repo, P., Icay, K., Ivaska, J., Saharinen, P., Hautaniemi, S., Lehti, K., & Ojala, P. M.
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2018-05-01
- Volume
- 7
- ISSN
- 2050-084X
- PMC
- PMC5929907
- Cited by
- 42
- References
- 1
- Language
- en
- Licence
- Funders
- Terveyden Tutkimuksen Toimikunta (307366, 309544)
- Finnish Cancer Foundation
- Sigrid Juséliuksen Säätiö
- University of Helsinki (Doctoral program in Biomedicine)
- University of Helsinki Foundation
- Suomen Lääketieteen Säätiö
- Emil Aaltosen Säätiö
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