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Tumour-derived SPARC drives vascular permeability and extravasation through endothelial VCAM1 signalling to promote metastasis
Open accessAbstract
Disruption of the endothelial barrier by tumour-derived secreted factors is a critical step in cancer cell extravasation and metastasis. Here, by comparative proteomic analysis of melanoma secretomes, we identify the matricellular protein SPARC as a novel tumour-derived vascular permeability factor. SPARC deficiency abrogates tumour-initiated permeability of lung capillaries and prevents extravasation, whereas SPARC overexpression enhances vascular leakiness, extravasation and lung metastasis. SPARC-induced paracellular permeability is dependent on the endothelial VCAM1 receptor and p38 MAPK signalling. Blocking VCAM1 impedes melanoma-induced endothelial permeability and extravasation. The clinical relevance of our findings is highlighted by high levels of SPARC detected in tumour from human pulmonary melanoma lesions. Our study establishes tumour-produced SPARC and VCAM1 as regulators of cancer extravasation, revealing a novel targetable interaction for prevention of metastasis. Metastatic cells are thought to influence vascular permeability through secreted factors but the mechanisms are unclear. Here, the authors identify melanoma-secreted SPARC as a major regulator of cancer cell extravasation that modulates endothelial intercellular junctions.
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Isolation and Characterization of Exosomes from Cell Culture Supernatants and Biological Fluids
Théry, C., Amigorena, S., Raposo, G., & Clayton, A. (2006) · Current Protocols in Cell Biology · doi:10.1002/0471143030.cb0322s30 · Cited by 5,766
Genes that mediate breast cancer metastasis to lung
Minn, A. J., Gupta, G. P., Siegel, P. M., Bos, P. D., Shu, W., Giri, D. D., Viale, A., Olshen, A. B., Gerald, W. L., & Massagué, J. (2005) · Nature · doi:10.1038/nature03799 · Cited by 2,922
Crossing the endothelial barrier during metastasis
Reymond, N., d'Água, B. B., & Ridley, A. J. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3628 · Cited by 922
PDK1 Regulates Cancer Cell Motility by Antagonising Inhibition of ROCK1 by RhoE
Pinner, S., & Sahai, E. (2008) · Nature Cell Biology · doi:10.1038/ncb1675 · Cited by 267
Cited by
Metastatic colonization by circulating tumour cells
Massagué, J., & Obenauf, A. C. (2016) · Nature · doi:10.1038/nature17038 · Cited by 2,062
Diversity and versatility of p38 kinase signalling in health and disease
Canovas, B., & Nebreda, A. R. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00322-w · Cited by 657
Surviving at a Distance: Organ-Specific Metastasis
Obenauf, A. C., & Massagué, J. (2015) · Trends in Cancer · doi:10.1016/j.trecan.2015.07.009 · Cited by 565
Unravelling tumour heterogeneity by single-cell profiling of circulating tumour cells
Keller, L., & Pantel, K. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0180-2 · Cited by 544
Passing the Vascular Barrier: Endothelial Signaling Processes Controlling Extravasation
Wettschureck, N., Strilic, B., & Offermanns, S. (2019) · Physiological Reviews · doi:10.1152/physrev.00037.2018 · Cited by 286
Metadata
- Authors
- Tichet, M., Prod’Homme, V., Fenouille, N., Ambrosetti, D., Mallavialle, A., Cerezo, M., Ohanna, M., Audebert, S., Rocchi, S., Giacchero, D., Boukari, F., Allegra, M., Chambard, J.-C., Lacour, J.-P., Michiels, J.-F., Borg, J.-P., Deckert, M., & Tartare-Deckert, S.
- Venue
- Nature Communications
- Published
- 2015-04-30
- Volume
- 6
- Issue
- 1
- Pages
- 6993-6993
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W1969706233
- Cited by
- 200
- References
- 4
- FWCI
- 10.94
- Type
- journal article
- Language
- en
- Open access
- gold
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- Tichet, M., Prod’Homme, V., Fenouille, N., Ambrosetti, D., Mallavialle, A., Cerezo, M., Ohanna, M., Audebert, S., Rocchi, S., Giacchero, D., Boukari, F., Allegra, M., Chambard, J.-C., Lacour, J.-P., Michiels, J.-F., Borg, J.-P., Deckert, M., & Tartare-Deckert, S. (2015). Tumour-derived SPARC drives vascular permeability and extravasation through endothelial VCAM1 signalling to promote metastasis. Nature Communications. https://doi.org/10.1038/ncomms7993
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
