Vasculogenic mimicry of human ovarian cancer cells: Role of CD147

Abstract

The term vasculogenic mimicry (VM) indicates the process by which aggressive tumor cells are able to generate in vitro non-endothelial cell-lined channels delimited by extracellular matrix. Although VM has been described in several human malignancies, the molecular basis of this phenomenon is not entirely understood. In the present study, we examined VM in two ovarian cancer cell lines with different invasion capability (CABA I, low invasion activity; SKOV3, high invasion activity). Specifically, we focused on the potential role played by CD147/extracellular MMP inducer, a membrane spanning molecule highly expressed in tumor cells, in VM. Previous studies have shown that CD147 may be involved in the progression of malignancies by regulating the expression of metalloproteinases in peritumoral stromal cells. In this study, we found significant correlations between expression of CD147 in ovarian cancer cell lines and tumor invasiveness, the activity of the proteases and the ability to form vascular channels. The treatment of SKOV3 cells with small interfering RNA against CD147 suppressed the ability of these cells to generate non-endothelial cell-lined channels. In contrast, transfection of CD147 cDNA into the CABA I cell line resulted in an increased tumor invasiveness and enabled the formation of vascular channels. Altogether, our data suggest that CD147 may play a critical role in VM of CABA I and SKOV3, human ovarian cancer cell lines.