Gamma-Klotho exhibits multiple roles in tumor growth of human bladder cancer.

ABSTRACT: Alpha-Klotho (KL?) and beta-Klotho (KL?) have recently been reported to correlate with cancer prognosis in some malignancies and we previously reported the association between KL?, KL?, and urothelial carcinoma of the bladder (UCB), indicating that KL? acts as a tumor promoter. However, the association between gamma-Klotho (KL?) and cancer prognosis remains unclear. In the present study, we evaluated the association between KL? and UCB. To evaluate the effect of KL? on human bladder cancer cell lines in vitro assays were performed. Exogenous KL? increased the ability of human bladder cancer cells to proliferate, migrate, invade, form colonies, and provide anchorage-independent growth potential. In in vivo assays, eighteen mice bearing xenografts inoculated using UM-UC-3, were randomly divided into three groups and treated with a small interfering RNA (siRNA) by intratumoral administration once a week for four weeks. Knockdown of KL? with siRNA led to a dramatic change in tumor growth and suggested that KL? had effects on tumor growth, including promotion of cell proliferation, inhibition of apoptosis, and enhancement of the epithelial-mesenchymal transition. To confirm the study, human tissue samples were used and patients were divided into two groups according to KL? expression level. High expression of KL? was significantly associated with higher stage and grade cancer and the presence of lymphovascular invasion compared to patients with lower expression of KL?. Our results suggest that KL? plays an important role in tumor invasion and progression and these results may lead to the development of new therapies and diagnostic methods for UCB.

SUBMITTER: Hori S 

PROVIDER: S-EPMC5929405 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature