Serpins promote cancer cell survival and vascular co-option in brain metastasis Journal Article
| Authors: | Valiente, M.; Obenauf, A. C.; Jin, X.; Chen, Q.; Zhang, X. H. F.; Lee, D. J.; Chaft, J. E.; Kris, M. G.; Huse, J. T.; Brogi, E.; Massagué, J. |
| Article Title: | Serpins promote cancer cell survival and vascular co-option in brain metastasis |
| Abstract: | Brain metastasis is an ominous complication of cancer, yet most cancer cells that infiltrate the brain die of unknown causes. Here, we identify plasmin from the reactive brain stroma as a defense against metastatic invasion, and plasminogen activator (PA) inhibitory serpins in cancer cells as a shield against this defense. Plasmin suppresses brain metastasis in two ways: by converting membrane-bound astrocytic FasL into a paracrine death signal for cancer cells, and by inactivating the axon pathfinding molecule L1CAM, which metastatic cells express for spreading along brain capillaries and for metastatic outgrowth. Brain metastatic cells from lung cancer and breast cancer express high levels of anti-PA serpins, including neuroserpin and serpin B2, to prevent plasmin generation and its metastasis-suppressive effects. By protecting cancer cells from death signals and fostering vascular co-option, anti-PA serpins provide a unifying mechanism for the initiation of brain metastasis in lung and breast cancers. © 2014 Elsevier Inc. |
| Keywords: | controlled study; human tissue; unclassified drug; human cell; nonhuman; mouse; cell death; cell survival; breast cancer; gene expression; cell infiltration; fas ligand; cell line; animal experiment; lung cancer; vascularization; cancer inhibition; tumor suppressor gene; nerve fiber; cancer cell; serine proteinase inhibitor; brain metastasis; paracrine signaling; stroma; inflammatory infiltrate; cell adhesion molecule; circulating tumor cell; plasmin; plasminogen activator; brain tissue; tumor invasion; microvascular endothelial cell; human; priority journal; article; l1 cell adhesion molecule; neuroserpin; serine proteinase inhibitor b2; brain capillary endothelial cell; vascular cooption |
| Journal Title: | Cell |
| Volume: | 156 |
| Issue: | 5 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2014-02-27 |
| Start Page: | 1002 |
| End Page: | 1016 |
| Language: | English |
| DOI: | 10.1016/j.cell.2014.01.040 |
| PROVIDER: | scopus |
| PMCID: | PMC3988473 |
| PUBMED: | 24581498 |
| DOI/URL: | |
| Notes: | Export Date: 2 April 2014 -- CODEN: CELLB -- Source: Scopus |
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