子宮体癌悪性形質の機能的特性を表現するRCAS1発現による子宮体癌治療に関する標準化の試み(<特集>第57回学術講演会シンポジウム: 子宮体癌の予後因子に基づいた治療戦略-その標準化を目指して-)

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RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is a membrane protein that can form oligomers through a coiled-coil structure in its C-terminal portion. RCAS1 acts as a ligand for a putative receptor present in various human cell lines and on normal peripheral lymphocytes. It inhibits in vitro growth of receptor-expressing cells and induces apoptotic cell death. RCAS1 was strongly expressed in uterine and ovarian malignancies, and RCAS1 expression has also been reported to correlate with tumor progression or the invasive tendency of uterine endometrial cancer. To clarify the clinical significance of RCAS1 in endometrial cancer, we examined the following : 1) the relationship between RCAS1 expression and clinicopathologic variables in endometrial cancer, 2) the mechanism of RCAS1 secretion, 3) the contribution of RCAS1 to exaggeration of tumor aggresiveness. Overexpression of RCAS1 was significantly correlated with stage (P=0.009), extent of myometrial invasion (P=0.043), and positive peritoneal cytologic results (P=0.017). Multivariate analysis revealed that RCAS1 expression and metastasis were clinically significant prognostic factors for the overall survival. RCAS1 is cleaved proteolytically by TPA as tumor necrosis factor-α and FasL are processed. Ectodomain shedding is induced by activation of mitogen-activated protein kinase. RCAS1 expression increased in relation to exaggerated growth potential in transplanted nude mice. These results suggest that RCAS1 may facilitate cancer cell invasion of connective tissue in endometrial cancer through 1) enhancement of tumor aggressive potency, and 2) evasion of antitumor immune surveillance by an apoptotic counterattack mechanism against lymphocytes. Acquisition of data concerning the molecular mechanisms for RCAS1 function and expression may allow us not only to understand aggressive properties but also to explore novel therapy targeting uterine endometrial cancer.
2005-11-01

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