CD151/PETA-3 membrane protein has been suggested to be involved in the malignant progression of cancer. We have examined the role of CD151 protein in invasion and metastasis of cancer cells by using CD151-transfected Meljuso human melanoma cells. Invasion into matrigel and in vivo metastatic activity of CD151-transfected cells was enhanced significantly when compared to control transfectant cells lacking CD151 expression. Among the invasion-related cellular activities examined, cell motility and matrix metalloproteinase-9 (MMP-9) production were shown to be considerably increased by CD151 expression. The enhancement of cell motility and MMP-9 production by CD151 expression was abolished by inhibitors specific to AP-1 activating signal transducers including EGF receptor, Protein kinase C, Src, Ras, p38 MAPK, and JNK, and siRNAs targeted to Src, p38 MAPK, and JNK. Also, more actively phosphorylated forms of Src, p38 MAPK, and c-jun were found in the CD151 transfectant cells than those in the control transfectant cells. Furthermore, AP-1 binding sites in MMP-9 gene promoter were indispensable for the induction of MMP-9 expression by CD151. In addition, CD151 on one cell was shown to bind to neighboring cells expressing CD151, indicating that CD151 is a homophilic cell surface interacting protein. These results suggest that homophilic interaction of CD151 provokes AP-1 activating signal transduction pathway in human melanoma cells, leading to enhanced cell motility and MMP-9 expression.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]