Candidate of metastasis 1 regulates in vitro growth and invasion of bladder cancer cells

Abstract

COM1 (candidate of metastasis 1) has been recently shown to influence the metastatic ability of cancer cells and disease progression of certain solid tumours. The role of COM1 in bladder cancer remains unknown. In the present study, we examined the expression of the COM1 protein in human bladder tissues, and also its effect on growth, adhesion, migration and invasion of human bladder cancer cells, in vitro. The expression of COM1 in human bladder tissues and bladder cancer cell lines was assessed at both the mRNA and protein levels using RT-PCR and immunohistochemistry, respectively. COM1 staining was compared with tumour staging. Mammalian COM1 expression construct and anti-COM1 ribozyme transgenes were used to generate sublines of human bladder cancer cells with differential expression of COM1. The effect of COM1 on cellular functions was examined in bladder cancer cells with which COM1 was overexpressed or knocked down using a variety of in vitro assays. In normal bladder tissues, stronger staining of COM1 was seen in the cytoplasm of normal urothelial cells. In contrast, the staining was notably weak or absent in cancer cells of tumour tissues and invasive tumours had significantly low levels of staining compared with non-invasive tumours (p=0.012). Knockdown of COM1 in bladder cancer cell lines resulted in an increase in cellular growth and invasion, while overexpression of COM1 suppressed invasiveness and growth of these cells. Further investigation revealed an increased apoptosis and upregulated p21 in bladder cancer cells when COM1 was overexpressed. COM1 is expressed at low levels in human bladder cancer and in particular in invasive bladder tumours. COM1 levels are inversely correlated with the invasiveness and growth of bladder cancer cells in vitro. Induced apoptosis and upregulation of p21 are indicated in the mechanism of COM1 inhibiting bladder cancer cell growth. It suggests that COM1 is a potential tumour suppressor in human bladder cancer.