Lung cancer secreted microvesicles: underappreciated modulators of microenvironment in expanding tumors.
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. Furthermore, they induce expression of several pro-angiopoietic factors 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.
Wysoczynski
Marcin
M
Stem Cell Biology Program at James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
Ratajczak
Mariusz Z
MZ
D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000818:Animals; D001672:Biocompatible Materials; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002633:Chemotaxis; D003094:Collagen; D018450:Disease Progression; D004338:Drug Combinations; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017370:Interleukin-11 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007797:Laminin; D053605:Leukemia Inhibitory Factor / Q000378:metabolism; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D053683:Oncostatin M / Q000378:metabolism; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D043925:Angiogenesis Inducing Agents; D001672:Biocompatible Materials; D004338:Drug Combinations; D017370:Interleukin-11; D016209:Interleukin-8; D047908:Intracellular Signaling Peptides and Proteins; C507837:LIF protein, human; D007797:Laminin; D053605:Leukemia Inhibitory Factor; C508351:OSM protein, human; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; D053683:Oncostatin M; C059485:matrigel; D003094:Collagen; D020780:Matrix Metalloproteinase 9