Tumor-derived microvesicles modulate the establishment of metastatic melanoma in a phosphatidylserine-dependent manner.
Exposure of phosphatidylserine (PS) on cellular membranes and membrane-derived microvesicles stimulates a number of anti-inflammatory responses involved in malignant processes. Herein we show that B16F10 cells, a highly metastatic melanoma cell line, produce large quantities of PS-containing microvesicles in vitro. Tumor microvesicles increased TGF-beta(1) production by cultured macrophages and, in vivo, enhanced the metastatic potential of B16F10 cells in C57BL/6 mice, both effects being reversed by annexin V. Most strikingly, microvesicles induced melanoma metastasis in BALB/c mice, which are normally resistant to this tumor cell line. Altogether, this is the first demonstration that tumor-derived microvesicles favor the establishment of melanoma metastasis in a PS-dependent manner, possibly by down-regulating the host's inflammatory and/or anti-tumoral immune responses.
Lima
Luize G
LG
Division of Experimental Medicine, National Cancer Institute, RJ, Brazil; Institute of Medical Biochemistry, Federal University of Rio de Janeiro, RJ, Brazil. lglima@bioqmed.ufrj.br
Chammas
Roger
R
Monteiro
Robson Q
RQ
Moreira
Maria Elisabete C
ME
Barcinski
Marcello A
MA
D000818:Animals; D045744:Cell Line, Tumor; D055252:Cell-Derived Microparticles / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D005434:Flow Cytometry; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008546:Melanoma, Experimental / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness / Q000276:immunology; D010718:Phosphatidylserines / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000276:immunology / Q000378:metabolism
D010718:Phosphatidylserines; D053773:Transforming Growth Factor beta1