Novel therapeutic strategies to target RCAS1, which induces apoptosis via ectodomain shedding.

Abstract

The expression of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is associated with aggressive characteristics and poor overall survival for 15 different human malignancies. The correlation between RCAS1 expression and several clinicopathological variables, including tumor size, clinical stage, invasion depth and lymph node metastasis highlights this molecule's clinical significance. RCAS1 is a biomarker because: (1) its concentration in serum or pleural effusion is significantly higher in cancer patients; (2) its level is associated with treatment response; and (3) high RCAS1-valued serum from cancer patients inhibits growth of RCAS1 putative receptor-expressing K562 cells. RCAS1 is secreted by ectodomain shedding and induces apoptosis in peripheral lymphocytes and natural killer (NK) cells. Although its putative receptor and mechanism of apoptosis induction remain undefined, RCAS1 is believed to help tumor cells evade immune surveillance. RCAS1 expression is also related to changes in extracellular matrix characteristics, reduction of vimentin-positive stromal cells, and increased microvessel density (MVD), all suggesting that RCAS1 may induce connective tissue remodeling. Further exploration of RCAS1 biological function will facilitate development of novel therapeutic strategies that target RCAS1.