Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 125, Issue 7, Pages 1595-1603Publisher
WILEY
DOI: 10.1002/ijc.24479
Keywords
lung cancer; tumor microvesicles; metastasis; angiogenesis; matrix metalloproteinases
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Funding
- NIH [R01 CA 106281-01]
- NATIONAL CANCER INSTITUTE [R01CA106281] Funding Source: NIH RePORTER
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Microvesicles (MVs) are shed from cell membranes of several cell types and have an important function in cell-to-cell communication. Exponentially growing lung cancer cells secrete large quantities of MVs and we were interested in their role in tumor progression. We observed that both human and murine lung cancer cell lines secrete more MVs in response to non-apoptotic doses of hypoxia and irradiation. These tumor-derived (t)MVs activate and chemoattract stroma fibroblasts and endothelial cells. Further-more, they induce expression of several pro-angiopoietic fa tors in stromal cells such as IL-8, VEGF, LIF, OSM, IL-11 and MMP-9. We also noticed that conditioned media harvested from stroma cells stimulated by tMVs enhanced the metastatic potential of both human and murine lung cancer cells in vivo. Thus, we postulated that tMVs are underappreciated constituents of the tumor microenvironment and play a pivotal role in tumor progression, metastasis and angiogenesis. (C) 2009 UICC
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