Targeting stanniocalcin‐1‐expressing tumor cells elicits efficient antitumor effects in a mouse model of human lung cancer. (7th April 2021) - Abe, Kotaro
Abstract: Lung cancer is the most common cause of cancer‐related death in developed countries; therefore, the generation of effective targeted therapeutic regimens is essential. Recently, gene therapy approaches toward malignant cells have emerged as attractive molecular therapeutics. Previous studies have indicated that stanniocalcin‐1 (STC‐1), a hormone involved in calcium and phosphate homeostasis, positively regulates proliferation, apoptosis resistance, and glucose metabolism in lung cancer cell lines. In this study, we investigated if targeting STC‐1 in tumor cells could be a promising strategy for lung cancer gene therapy. We confirmed that STC‐1 levels in peripheral blood were higher in lung cancer patients than in healthy donors and that STC‐1 expression was observed in five out of eight lung cancer cell lines. A vector expressing a suicide gene, uracil phosphoribosyltransferase (UPRT), under the control of the STC‐1 promoter, was constructed (p P STC‐1 ‐UPRT) and transfected into three STC‐1‐positive cell lines, PC‐9, A549, and H1299. When stably transfected, we observed significant cell growth inhibition using 5‐fluorouracil (5‐FU) treatment. Furthermore, growth of the STC‐1‐negative lung cancer cell line, LK‐2 was significantly arrested when combined with STC‐1‐positive cells transfected with p P STC‐1 ‐UPRT. We believe that conferring cytotoxicity in STC‐1‐positive lung cancer cells using a suicide gene may be a useful therapeutic strategy for lung cancer. Abstract : In this study, we observed that sera collected from lung cancer patients contained higher level of stanniocalcin‐1 (STC‐1), a hormone maintaining mineral homeostasis, than those from healthy donors. In addition, we showed that effective anti‐tumor effect was obtained by targeting lung cancer cells which express STC‐1. This study elucidated that STC‐1 could be useful as both a molecular target and as a marker for lung cancer.