Manufacture of novel RCAS1-targeting therapy against gynecologic cancer

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RCAS1 expression is significantly related to overall survival of patients with various cancers. RCAS1 is secreted and induces apoptosis in putative receptor expressing cells including immune cells such as peripheral lymphocytes and NK cells. To clarify the biological significance of RCAS1, we here investigated 1) the association between RCAS1 expression and tumor growth potential, and 2) mechanisms of RCAS1 secretion. 1) Knockdown of RCAS1 expression by siRNA significantly suppressed in vivo growth of SiSo and HOUA tumor cells. .Enhanced RCAS1 expression significantly promoted in vivo growth of tumors derived from COS-7 cells. Introduction of the RCAS1-encoding gene increased expression of VEGF. In uterine cervical cancer, RCAS1 expression was significantly 'associated with VEGF expression and microvessel density. 2) Uterine and ovarian cancer patients had significantly higher serum RCAS1 concentrations than did healthy blood donors. RCAS1 values were also significantly associated with response to treatment. The WST-1 assay showed that patients' serum induced K562 cell growth inhibition, but this effect partially recovered after immunodepletion of RCAS1. Therefore, RCAS1 may be a biomarker of gynecologic cancer. RCAS1 was secreted by ectodomain shedding via PKC-σ, Ras-MAPK, and transactivation pathways. Acquisition of data about the molecular mechanisms related to RCAS1 biological significance may allow us to explore novel therapies against gynecologic cancer.