WISP1 is the stromal-secreting oncoprotein via paracrine downregulation of NDRG1, KAI1, and Maspin in human bladder cancer cells

WNT1 inducible signaling pathway protein 1 (WISP1) is a connective tissue growth factor that regulates various cellular functions in different tissues but has yet to be examined in the human bladder. Two isoforms of WISP1 (WISP1v1 and WISP1v2) expressed only in bladder fibroblast (HBdSF) and smooth muscle (HBdSMC) cells but not in bladder cancer cells in vitro. TNF-α treatment-induced IL-6, CXCL5, and SDF-1 expressions in bladder stroma cells. TNF-α-induced IL-6 depends on the WISP1, and the TNF-α-activation was suppressed under CAPE treatment. WISP1-knockdown inhibited the proliferation and contraction of HBdSMC and HBdSF cells, while the conditioned media from either ectopic WISP1v1- or WISP1v2-overexpressed 293T cells stimulated both the proliferation of HBdSF and HBdSMC cells. The supernatant of WISP1-knockdown in HBdSMC cells reduced the migration of bladder carcinoma T24 cells. WISP1v1, but not WISP1v2, enhanced cell growth, migration, and invasion in bladder cancer cells via downregulating NDRG1, KAI1, and Maspin expressions. Silico's analysis confirmed that WISP1 is a potential oncogene in human bladder cancer. Results suggest that WISP1, a stroma-specific secreted protein, modulates the behavior of bladder stroma cells via autocrine signaling. WISP1 induces tumor growth of bladder carcinoma cells in an isoform-dependent manner via paracrine signaling, indicating that WISP1 may behave as a mediator linking diseases of the human bladder.