Ectopic expression of KLK6 in MDA-MB-435 melanoma cells reduces tumorigenicity in vivo.

Melanoma is an aggressive form of cancer with poor prognosis therefore, identification of associated pathophysiological mechanisms is imperative towards the development of new therapeutic strategies. The KLK6 is a serine protease normally expressed in the epidermis. Recently, we found that elimination of Klk6 in mice results in enhanced resistance to chemically induced non-melanoma skin cancer. To delineate putative roles of KLK6 in melanoma, the invasive KLK6-non-expressing MDA-MB-435 melanoma cell line was stably transfected with the full-length KLK6 cDNA and expression of the corresponding RNA and protein were confirmed. Interestingly, restoration of KLK6 expression resulted in markedly suppressed growth of primary tumors when orthotopically implanted in SCID mice. Analysis of data retrieved from the human protein atlas revealed that melanomas with high KLK6 expression have a trend for longer survival. Collectively, we suggest that KLK6 inhibits growth of melanomas.