Apoptotic function of tumor-associated antigen RCAS1 in oral squamous cell carcinoma
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RESEARCH
Open Access
Apoptotic function of tumor-associated antigen RCAS1 in oral squamous cell carcinoma Hideaki Tanaka1, Takeshi Toyoshima1*, Kenzo Sonoda2, Ryoji Kitamura1, Masaaki Sasaguri3, Shintaro Kawano1, Ryota Matsubara1, Yuichi Goto1 and Seiji Nakamura1
Abstract Background: Receptor-binding cancer antigen expressed on SiSo cell (RCAS1) is derived from uterine adenocarcinoma and can induce apoptosis in lymphocytes, allowing tumor cells to escape from immune surveillance. RCAS1 is reportedly expressed in a membranous pattern on tumor cell or soluble one in serum of patients. The aim of this study was to investigate expression patterns of RCAS1 and the effect on apoptosis in oral squamous cell carcinoma (OSCC) cell lines. Methods: In four kinds of OSCC cell lines (HSC-2, HSC-3, SQUU-A, and SQUU-B), RCAS1 mRNAs and proteins were determined by RT-PCR and immunocytochemistry. Membranous RCAS1 was determined by flow cytometry. Culture supernatants were analyzed for detection of soluble RCAS1 by dot blotting and enzyme-linked immunosorbent assay. Apoptotic ability of RCAS1 on the erythroid leukemia cell line K562 with the putative receptor was evaluated by flow cytometry in co-culture with highly metastatic SQUU-B, with knocked-down RCAS1 cells or in a no-cell contact condition. Results: RCAS1 mRNA and proteins were expressed in all of OSCC cell lines. Membranous pattern were expressed in all cell lines, while soluble pattern was detected in all supernatants. RCAS1 mRNA, membranous and soluble RCAS1 were significantly seen in SQUU-B more than the other 3 cell lines (P < 0.05). K562 apoptosis was induced in co-culture with each of all cell lines, particularly with SQUU-B. Apoptosis was markedly reduced in co-culture with RCAS1 knockdown cells, but was induced in co-culture without cell contract of SQUU-B. Conlusions: Our study suggests that RCAS1 has an apoptotic function via membranous/soluble expression pattern in OSCC cells. RCAS1 may thus affect tumor escape from immune surveillance in OSCC by inducing apoptosis. Keywords: RCAS1, Oral squamous cell carcinoma, Apoptosis, Immune surveillance, Biomarker
Background Receptor-binding cancer antigen expressed on SiSo cell (RCAS1) is recognized by the monoclonal antibody 22-1-1, and was initially identified in uterine adenocarcinoma [1,2]. Its expression is reportedly correlated with clinicopathological parameters in 15 human cancers, such as clinical stage, histological subtype, differentiation, tumor size, depth of invasion, lymphovascular space involvement, lymph node metastasis, and cytological results [3-20]. RCAS1 acts as a ligand for a putative receptor in cell lines of several human tissue types and peripheral lymphocytes, such as activated T, B, and NK cells. In vitro, RCAS1 * Correspondence: [email protected] 1 Division of Maxillofacial Diagnostic and Surgical Sciences, Section of Oral and Maxillofacial Oncology, Faculty of Dental Science, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan Full list of author information is
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