Millimaggi Danilo, Mari Marianna, D'Ascenzo Sandra, Carosa Eleonora, Jannini Emmanuele Angelo, Zucker Stanley, Carta Gaspare, Pavan Antonio, Dolo Vincenza
Department of Experimental Medicine, L'Aquila University, L'Aquila, Italy.
Neoplasia. 2007 Apr;9(4):349-57. doi: 10.1593/neo.07133.
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.
细胞外基质的基质金属蛋白酶（MMP）降解被认为在侵袭、血管生成、肿瘤生长和转移中起重要作用。多项研究表明，CD147/细胞外MMP诱导剂是一种在肿瘤细胞中高度表达的跨膜分子，可能通过调节肿瘤周围基质细胞中MMP的表达参与恶性肿瘤的进展。在本研究中，我们发现CD147在源自上皮性卵巢癌细胞的微泡中表达，且CD147阳性微泡可能在体外促进内皮细胞的血管生成表型。人卵巢癌细胞系OVCAR3、SKOV3和A2780释放的微泡表达不同水平的CD147，并以CD147依赖的方式刺激人脐静脉内皮细胞（HUVECs）的促血管生成活性（OVCAR3 > SKOV3 > A2780）。此外，CD147表达低的卵巢癌细胞系CABA I释放的微泡对HUVECs血管生成表型的发展没有显著影响。用针对CD147的小干扰RNA处理OVCAR3细胞可抑制OVCAR3衍生微泡的血管生成潜力。然而，将CD147 cDNA转染到CABA I细胞系中可使CABA I衍生的微泡诱导血管生成并促进HUVECs中MMP基因的表达。因此，我们得出结论，卵巢癌细胞释放的微泡可能通过CD147介导的机制诱导HUVECs的促血管生成活性。
