The Level of RCAS1 Expression Is Inversely Correlated With the Number of Vimentin-Positive Stromal Cells in Epithelial Ovarian Cancer

Abstract

Expression of RCAS1 is significantly associated with clinical prognosis in 15 different types of human cancer. We have previously reported that RCAS1 expression is correlated with a decreasing number of vimentin-positive stromal cells in cervical cancer. Moreover, RCAS1 expression is related to the expression of matrix metalloprotease 1 and laminin 5 and angiogenesis. We examined whether RCAS1 contributes to connective tissue remodeling in epithelial ovarian cancer. RCAS1 expression was studied retrospectively via immunohistochemistry. Samples were obtained from resected tumor tissues from 65 patients with epithelial ovarian cancer. Statistical analysis was done to correlate RCAS1 expression and clinicopathologic variables. The associations between RCAS1 expression and the number of vimentin-positive cells or microvessel density were evaluated. Western blot analysis was also performed to verify the perturbation of vimentin expression in fibroblast L cells, following stimulation by soluble RCAS1. RCAS1 expression was detected in 72.3% (47/65 total cases) and significantly correlated with age and histological subtype. Patients with advanced stage, positive lymph node metastasis, or positive peritoneal cytological results had significantly shorter overall survival rates; however, no significant relationship was detected between RCAS1 immunoreactivity and overall survival. In the connective tissue surrounding tumor cells, the number of cells expressing vimentin significantly decreased in relation to the RCAS1 expression level. The growth of L cells was suppressed after stimulation by soluble RCAS1, and the expression of vimentin was markedly diminished. RCAS1 may contribute to connective tissue remodeling by altering the number of vimentin-positive cells in epithelial ovarian cancer.

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

“…RCAS1 was secreted by ectodomain shedding through an activation of the MAPK pathway. Overexpression and ectodomain shedding of RCAS1 may contribute to tumor progression via not only stromal remodeling but also tumor cell proliferation [28][29][30].…”

The Analysis of Receptor-binding Cancer Antigen Expressed on SiSo Cells (RCAS1) immunoreactivity within the microenvironment of the ovarian cancer lesion relative to the applied therapeutic strategy

“…The infiltration of these cells corresponds to cancer progression (Dutsch-Wicherek et al 2009). RCAS1-positive macrophages were not detected in the ovarian cancer microenvironment, although RCAS1 was observed in both the cytoplasm and membrane of ovarian cancer cells within the cancer nest (Akahira et al 2004; Sonoda et al 2008; 2009). Moreover, RCAS1 expression in the cancer nest was higher in those patients who had advanced ovarian cancer (Akahira et al 2004).…”

“…Recently, Sonoda et al . found that the level of RCAS1 correlates inversely with the number of Vimentin positive cells within the microenvironment of the ovarian cancer (Sonoda et al 2009). These cells participate in connective tissue remodeling, which is in turn directly linked with overall survival rates.…”

“…In his study, Sonoda demonstrated that, while on the one hand, the intensity of the RCAS1 immunoreactivity in ovarian cancer cells was related to a poor prognosis for the case (Sonoda et al 2009), on the other hand, the presence of RCAS1 expression within the cervical cancer microenvironment was associated with the potential to develop metastases (Sonoda et al 2005a; 2007). The participation of RCAS1 in the development of metastases was also found in other types of adenocarcinoma (Dutsch-Wicherek et al 2009; Iwasaki et al 2000; Nakabayashi et al 2007).…”

Apoptotic function of tumor-associated antigen RCAS1 in oral squamous cell carcinoma

“…Therefore, highly metastatic OSCC cells are likely to express RCAS1 as membranous or soluble proteins. In cervical and ovarian cancers, the number of cells that express mesenchymal marker vimentin is inversely related to RCAS1 expression, as remodeling of stromal tissue by vimentin results in tumor invasion and metastasis [35]. Moreover, enhanced RCAS1 expression in African Green Monkey kidney fibroblast cell lines COS-7 following introduction of the RCAS1 gene significantly promotes in vivo tumor growth via increase of vascular endothelial growth factor [36], which implies that RCAS1 affects tumor progression through lymph nodal metastasis.…”