The biological role of the unique molecule RCAS1: a bioactive marker that induces connective tissue remodeling and lymphocyte apoptosis

Abstract

RCAS1 is a receptor-binding cancer antigen which is expressed on human uterine cervical adenocarcinoma cell line (SiSo). Finding a correlation between the expression of this gene and the overall survival of patients with 14 different types of cancer points to the clinical significance of this gene. Moreover, the expression RCAS1 correlates with other clinicopathological parameters including the histological type of cancer, its differentiation, tumor size, clinical stage, the depth of invasion, lymphovascular space involvement, lymph node metastasis, and positive peritoneal cytological results. RCAS1 can induce apoptosis in peripheral lymphocytes in vitro as well as in an increased number of apoptotic tumor-infiltrating lymphocytes. RCAS1 is also believed to contribute to the escape of tumor cells from immune surveillance. RCAS1 is secreted via ectodomain shedding, and its expression is related to changes in the characteristics of the extracellular matrix and to a reduced number of vimentin-positive tumor stromal cells, findings that suggest that RCAS1 may induce connective tissue remodeling. The concentration of RCAS1 in serum or pleural effusions has been found to be significantly higher in patients with several different types of cancer as compared to normal controls. Together, the available data shows that RCAS1 may have value as a biomarker for monitoring therapeutic efficacy. Further exploration of the biological function of RCAS1 should help in the development of new therapeutic strategies against human malignancies.

Diagnostic value of soluble receptor-binding cancer antigen expressed on SiSo cells and carcinoembryonic antigen in differentiating malignant from benign pleural effusion

“…In NSCLC cases with high RCAS1 expression, the apoptotic index of tumor-infiltrating lymphocytes was significantly higher than those with low expression [17]. Therefore, upregulation of RCAS1 expression may play a crucial role in tumor progression by enabling cancer cells to escape from immune surveillance [13,[25][26][27]. Additionally, RCAS1 was also shown to facilitate tumor cell invasion of connective tissue by induction of tumor microenvironment remodeling.…”

The tumour and its microenvironment – a complicated interplay

“…As shown in our studies, macrophages of this type demonstrate strong expression of the RCAS1 protein [10]. The protein, as studies by Sonoda et al [11] suggest, may play a major role in suppressing the immune response targeted against the tumour.…”

RCAS-1 Serum and Tumor Levels in Head and Neck Squamous Cell Carcinoma

“…RCAS-1 has been found to facilitate tumor immune escape [1] . Based on this one would expect higher protein levels in malignant than in premalignant and healthy tissue.…”