Roles of a metastasis-associated molecule, RTVP-1, in cancer immunosurveillance

ObjectiveTo elucidate distinct functions of a recently identified cancer metastasis-associated molecule, related to testes-specific, vespid, and pathogenesis protein-1 (RTVP-1) in the mammalian immune system.MethodsImmunohistochemical assays and functional analysis on the immune system were performed on RTVP–/– mice and RTVP-1+/+ mice. Protein-protein interaction (PPI) was used to predict the functions of RTVP-1.ResultsAbnormal lymphocyte growth kinetics and reduced numbers of CD8+ T cells were revealed in lymph nodes of RTVP-1–/– mice. Expression of phenotypic markers of maturation in bone marrow-derived dendritic cells (DC) was impaired in RTVP-1–/– DC following antigenic stimulation in vitro and RTVP-1–/– DC failed to provide normal CD4+ T cell stimulatory activities in vivo. RTVP-1–/– mice failed to generate normal CTL or antibody responses in vivo after vaccination. In vivo tumor challenge experiments using a mouse cancer cell line demonstrated that the growth rate of subcutaneous tumors in RTVP-1–/– mice was significantly increased and CD8+ T cell infiltration significantly reduced compared to RTVP-1+/+ mice. PPI showed that RTVP-1 protein closely interacted with molecules associated with immune response and cancer metastasis.ConclusionRTVP-1 might function as a tumor metastasis suppressor and immunosurveillance molecule in cancer.