The membrane molecule RCAS1 induces immune cell apoptosis via the RCAS1-RCAS1R pathway

Zhang,Yuanyuan; Zhu,Jie; Hong,Xuejun; Zhou,Yunlian; Ren,Keming; Shu,Xiaoli; Wang,Qingqing

doi:10.3892/ijmm.2013.1326

The membrane molecule RCAS1 induces immune cell apoptosis via the RCAS1-RCAS1R pathway

Authors:
- Yuanyuan Zhang
- Jie Zhu
- Xuejun Hong
- Yunlian Zhou
- Keming Ren
- Xiaoli Shu
- Qingqing Wang
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Affiliations: The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310031, P.R. China, Clinical Laboratory of Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China, Xuancheng Blood Center, Xuancheng, Anhui 242000, P.R. China, Institute of Immunology, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China
Published online on: April 3, 2013 https://doi.org/10.3892/ijmm.2013.1326
Pages: 1319-1326

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Abstract

Tumor-associated antigen receptor-binding cancer antigen expressed on SiSo cells (RCAS1) has been identified as an estrogen-responsive gene and reportedly acts as a ligand for a putative receptor present in a variety of human cell lines and peripheral lymphocytes, thus leading them to apoptosis. In this study, we investigated the biological function of RCAS1 in vitro in inducing the apoptosis of immune cells. We detected the expression of the RCAS1 receptor (RCAS1R) in the cell lines, and investigated the mechanisms behind the apoptosis induced by RCAS1. HeLa cells were transfected with recombinant adenovirus Ad-RCAS1. RCAS1 induced the apoptosis of activated T cells, K562 cells and phytohemagglutinin (PHA)-activated Jurkat cells via the RCAS1-RCAS1R pathway. The expression of RCAS1R was induced. The intracellular overexpression of RCAS1 inhibited the growth of Jurkat and K562 cells. The expression of RCAS1 negatively correlated with the expression of glycogen synthase kinase 3β (GSK3β), but positively correlated with the expression of phosphorylated GSK3β (phGSK3β). RCAS1 expression was identified as a brown staining pattern in the breast cancer specimens. These findings may provide insight into the mechanisms through which tumor cells escape from immune surveillance.

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1	Tsuchiya F, Ikeda K, Tsutsumi O, et al: Molecular cloning and characterization of mouse EBAG9, homolog of a human cancer associated surface antigen: expression and regulation by estrogen. Biochem Biophys Res Commun. 284:2–10. 2001. View Article : Google Scholar
2	Suzuki T, Inoue S, Kawabata W, et al: EBAG9/RCAS1 in human breast carcinoma: a possible factor in endocrine-immune interactions. Br J Cancer. 85:1731–1737. 2001. View Article : Google Scholar : PubMed/NCBI
3	Akahira JI, Aoki M, Suzuki T, et al: Expression of EBAG9/RCAS1 is associated with advanced disease in human epithelial ovarian cancer. Br J Cancer. 90:2197–2202. 2004. View Article : Google Scholar : PubMed/NCBI
4	Takahashi S, Urano T, Tsuchiya F, et al: EBAG9/RCAS1 expression and its prognostic significance in prostatic cancer. Int J Cancer. 106:310–315. 2003. View Article : Google Scholar : PubMed/NCBI
5	Aoki T, Inoue S, Imamura H, et al: EBAG9/RCAS1 expression in hepatocellular carcinoma: correlation with tumour dedifferentiation and proliferation. Eur J Cancer. 39:1552–1561. 2003. View Article : Google Scholar : PubMed/NCBI
6	Nakashima M, Sonoda K and Watanabe T: Inhibition of cell growth and induction of apoptotic cell death by the human tumor-associated antigen RCAS1. Nat Med. 5:938–942. 1999. View Article : Google Scholar : PubMed/NCBI
7	Matsushima T, Nakashima M, Oshima K, et al: Receptor binding cancer antigen expressed on SiSo cells, a novel regulator of apoptosis of erythroid progenitor cells. Blood. 98:313–321. 2001. View Article : Google Scholar : PubMed/NCBI
8	Sonoda K, Miyamoto S, Yamazaki A, Kobayashi H, Nakashima M, Mekada E and Wake N: Biologic significance of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) as a pivotal regulator of tumor growth through angiogenesis in human uterine cancer. Cancer. 110:1979–1990. 2007. View Article : Google Scholar
9	Oshikiri T, Miyamoto M, Morita T, et al: Tumor-associated antigen recognized by the 22-1-1 monoclonal antibody encourages colorectal cancer progression under the scanty CD8⁺ T cells. Clin Cancer Res. 12:411–416. 2006. View Article : Google Scholar
10	Chatterjee M, Mohapatra S, Ionan A, et al: Diagnostic markers of ovarian cancer by high-throughput antigen cloning and detection on arrays. Cancer Res. 66:1181–1190. 2006. View Article : Google Scholar : PubMed/NCBI
11	Hong XJ, Shen FP and Wang QQ: Construction of recombinant GST-RCAS1 fusion gene and its expression in E. Coli. Zhejiang Da Xue Xue Bao Yi Xue Ban. 35:377–383. 2006.(In Chinese).
12	Hong X, Liu Y, Hu G, et al: EBAG9 inducing hyporesponsiveness of T cells promotes tumor growth and metastasis in 4T1 murine mammary carcinoma. Cancer Sci. 100:961–969. 2009. View Article : Google Scholar : PubMed/NCBI
13	Reed LJ and Muench HA: A simple method for estimating fifty percent endpoint. Am J Hyg. 27:493–497. 1938.
14	Engelsberg A, Hermosilla R, Karsten U, Schülein R, Dörken B and Rehm A: The Golgi protein RCAS1 controls cell surface expression of tumor-associated O-linked glycan antigens. J Biol Chem. 278:22998–23007. 2003. View Article : Google Scholar : PubMed/NCBI
15	Reimer TA, Anagnostopoulos I, Erdmann B, et al: Reevaluation of the 22-1-1 antibody and its putative antigen, EBAG9/RCAS1, as a tumor marker. BMC Cancer. 5:472005. View Article : Google Scholar : PubMed/NCBI
16	Embi N, Rylatt DB and Cohen P: Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase. Eur J Biochem. 107:519–527. 1980. View Article : Google Scholar : PubMed/NCBI
17	Woodgett JR and Cohen P: Multisite phosphorylation of glycogen synthase. Molecular basis for the substrate specificity of glycogen synthase kinase-3 and casein kinase-II (glycogen synthase kinase-5). Biochim Biophys Acta. 788:339–347. 1984.
18	Jope RS and Johnson GV: The glamour and gloom of glycogen synthase kinase-3. Trends Biochem Sci. 29:95–102. 2004. View Article : Google Scholar : PubMed/NCBI
19	Hoeflich KP, Luo J, Rubie EA, Tsao MS, Jin O and Woodgett JR: Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation. Nature. 406:86–90. 2000. View Article : Google Scholar : PubMed/NCBI
20	Martin M, Rehani K, Jope RS and Michalek SM: Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3. Nat Immunol. 6:777–784. 2005. View Article : Google Scholar : PubMed/NCBI
21	Dutsch-Wicherek M and Wicherek L: The association of RCAS1 serum concentration with the reversibility or irreversibility of the process of immune cytotoxic activity restriction during normal menstrual cycle, cancer relapse, and surgical treatment for various types of squamous cell carcinomas and adenocarcinomas. Am J Reprod Immunol. 59:266–275. 2008.
22	Dutsch-Wicherek M, Tomaszewska R, Lazar A, Wicherek L and Skladzien J: The association between RCAS1 expression in laryngeal and pharyngeal cancer and its healthy stroma with cancer relapse. BMC Cancer. 28:9–35. 2009.PubMed/NCBI