Tumor vesicle-associated CD147 modulates the angiogenic capability of endothelial cells.
Matrix metalloproteinase (MMP) degradation of extracellular matrix is thought to play an important role in invasion, angiogenesis, tumor growth, and metastasis. Several studies have demonstrated that CD147/extracellular MMP inducer, a membrane-spanning molecule highly expressed in tumor cells, may be involved in the progression of malignancies by regulating expression of MMP in peritumoral stromal cells. In the present study we show that CD147 is expressed in microvesicles derived from epithelial ovarian cancer cells and that CD147-positive vesicles may promote an angiogenic phenotype in endothelial cells in vitro. Vesicles shed by human ovarian carcinoma cell lines OVCAR3, SKOV3, and A2780 expressed different levels of CD147 and stimulated proangiogenic activities of human umbilical vein endothelial cells (HUVECs) in a CD147-dependent fashion (OVCAR3 > SKOV3 > A2780). Moreover, vesicles shed by ovarian carcinoma cell line CABA I with low CD147 expression had no significant effect on the development of angiogenic phenotype in HUVECs. The treatment of OVCAR3 cells with small interfering RNA against CD147 suppressed the angiogenic potential of OVCAR3-derived microvesicles. However, transfection of CD147 cDNA into the CABA I cell line enabled CABA I-derived vesicles to induce angiogenesis and to promote MMP genes expression in HUVECs. We therefore conclude that vesicles shed by ovarian cancer cells may induce proangiogenic activities of HUVECs by a CD147-mediated mechanism.
Millimaggi
Danilo
D
Department of Experimental Medicine, L'Aquila University, L'Aquila, Italy.
Mari
Marianna
M
D'Ascenzo
Sandra
S
Carosa
Eleonora
E
Jannini
Emmanuele Angelo
EA
Zucker
Stanley
S
Carta
Gaspare
G
Pavan
Antonio
A
Dolo
Vincenza
V
D051926:Basigin / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D022162:Cytoplasmic Vesicles / Q000378:metabolism / Q000473:pathology*; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*
D051926:Basigin