Department of Pharmacy, School of Health Sciences, University of Patras, Rion-Patras, 265 04, Greece.
National Hellenic Research Foundation, Athens, 116 35, Greece.
Pathol Res Pract. 2021 Jan;217:153276. doi: 10.1016/j.prp.2020.153276. Epub 2020 Nov 14.
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.
黑色素瘤是一种预后不良的侵袭性癌症，因此，确定相关的病理生理机制对于开发新的治疗策略至关重要。KLK6 是一种丝氨酸蛋白酶，通常在表皮中表达。最近，我们发现敲除 Klk6 的小鼠对化学诱导的非黑色素瘤皮肤癌具有更强的抵抗力。为了阐明 KLK6 在黑色素瘤中的潜在作用，我们将全长 KLK6 cDNA 稳定转染到侵袭性 KLK6 不表达的 MDA-MB-435 黑色素瘤细胞系中，并证实了相应的 RNA 和蛋白质的表达。有趣的是，当将 KLK6 表达恢复的 MDA-MB-435 细胞系原位植入 SCID 小鼠时，其原发性肿瘤的生长明显受到抑制。从人类蛋白质图谱中检索到的数据的分析表明，KLK6 高表达的黑色素瘤具有延长生存期的趋势。总的来说，我们认为 KLK6 抑制黑色素瘤的生长。
