Panoply™ Human BSG Over-expressing Stable Cell Line

CD147 (also known as BSG or EMMPRIN) is a transmembrane protein that induces the expression and activity of matrix metalloproteinases (MMPs). CD147 expression has been shown to enhance cancer cell migration, invasion, and metastasis. Here, researchers used CD147-overexpressing cholangiocarcinoma (CCA) cells to elucidate the critical role of CD147 in metastasis in vitro and in vivo. They generated five CD147-overexpressing clones (Ex-CD147) from the CD147-low-expressing CCA cell line KKU-055. All Ex-CD147 clones exhibited high CD147 expression and liver colonization in a mouse model injected via tail vein, whereas the parental cells lacked this ability. Ex-CD147 clones displayed a metastatic phenotype (i.e., increased F-actin rearrangement) and decreased cell invasion and adhesion. The molecular mechanism underlying this effect was demonstrated to be through induction of MMP-2 activity and enhanced epithelial-mesenchymal transition. Increased expression of the mesenchymal markers Slug, vimentin, and N-cadherin, as well as decreased expression of the epithelial markers E-cadherin and Claudin-1, were observed in Ex-CD147 clones, along with suppression of the adhesion molecule ICAM-1. Furthermore, inhibition of CD147 expression using siCD147 in two cholangiocarcinoma (CCA) cell lines with high CD147 expression significantly reduced the migration and invasion capabilities of these CCA cells. These findings highlight the important role of CD147 in CCA metastasis and suggest that CD147 is a promising target for effective CCA therapy.

The researchers studied the effect of CD147 on cell migration and invasion in vitro. Unfortunately, the adhesion of CD147-overexpressing cells was low, so the migration capacity data obtained by the scratch test and Boyden chamber assay could not be used. Therefore, the researchers instead performed 3D invasion or evasion experiments. The results showed that all CD147-overexpressing cells had significantly higher invasive capacity compared with KKU-055 parental cells (Figure 1A). To explore the potential mechanism by which CD147 promotes cell invasion, they identified the downstream targets of CD147, MMP-2, and MMP-9 involved in cancer cell invasion. Gelatin zymography analysis showed that the MMP-2 activity of CD147-overexpressing cells was significantly higher than that of their parental cells (Figure 1B). Western blot analysis of epithelial markers (E-cadherin and Claudin-1) and mesenchymal markers (N-cadherin, vimentin, and Slug) showed that CD147-overexpressing cells expressed lower levels of E-cadherin and Claudin-1 and higher levels of N-cadherin, vimentin, and Slug than their parental cells (Figure 1C).

Figure 1. Overexpression of CD147 promotes invasion by stimulating MMP-2 and the epithelial-to-mesenchymal transition process in CCA cells. (Dana P, et al., 2017)