Serpins Promote Cancer Cell Survival and Vascular Cooption in Brain Metastasis
By M. Valiente, A. Obenauf, Xin Jin, Qing Chen, X. Zhang, Derek J. Lee, J. Chaft, M. Kris, Jason T. Huse, E. Brogi and 1 more. Cell, 2014
825 citations recorded by the source corpus.
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 that 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 deleterious consequences. By protecting cancer cells from death signals and fostering vascular cooption, anti-PA serpins provide a unifying mechanism for the initiation of brain metastasis in lung and breast cancers.
Subfields: Cancer Research, Molecular Biology, Physiology
View Paper: https://www.semanticscholar.org/paper/0946b27e1b590a9f0c91387b415a99ea14b1a395
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In Cancer Research
In Molecular Biology
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Citations in the corpus
- EMERGING BIOLOGICAL PRINCIPLES OF METASTASIS (2017, neutral): “In the brain, for example, cancer cells encounter reactive astrocytes that produce plasminogen activator, leading to the production of plasmin that induces carcinoma cell death (Valiente et al., 2014).”
- Metastatic Stem Cells: Sources, Niches, and Vital Pathways (2014, background): “Image adapted from Valiente et al. (2014). Cell Stem Cell”
- Integrin Signaling in Cancer: Mechanotransduction, Stemness, Epithelial Plasticity, and Therapeutic Resistance (2019, background): “abluminal surface of blood vessels and outgrow by vascular cooption (Valiente et al., 2014).”
- The Cancer Stem Cell Niche: How Essential is the Niche in Regulating Stemness of Tumor Cells? (2015, neutral): “Interestingly, in models of brain metastasis from breast and lung cancers, brain stroma takes an active role in killing the infiltrating cancer cells (Valiente et al., 2014).”