Expression of Tumor-Associated Membrane Antigen, RCAS1, in Human Colorectal Carcinomas and Possible Role in Apoptosis of Tumor-Infiltrating Lymphocytes

Okada, Ken-ichi; Nakashima, Mitsuyoshi; Komuta, Ko; Hashimoto, Shinichi; Okudaira, Sadayuki; Baba, Naomichi; Hishikawa, Yoshitaka; Koji, Takehiko; Kanematsu, Takashi; Watanabe, Takeshi

doi:10.1097/01.mp.0000074732.17945.6c

Cited by 25 publications

(26 citation statements)

References 29 publications

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“…RCAS1 is up-regulated both in serum and tumor tissues in the later stages of colorectal cancer (20). Some evidence suggests that RCAS1 may negatively affect the prognosis of human colorectal cancer (24). Our data also suggest that Tn expression significantly affected overall survival.…”

Section: Discussionsupporting

confidence: 69%

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Tumor-Associated Antigen Recognized by the 22-1-1 Monoclonal Antibody Encourages Colorectal Cancer Progression under the Scanty CD8+ T Cells

Oshikiri¹,

Miyamoto²,

Morita³

et al. 2006

Clinical Cancer Research

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Purpose:The receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a novel tumorassociated antigen. Although evidence suggests that RCAS1 suppresses immunity by inducing tumor-infiltrating lymphocyte (TIL) apoptosis, RCAS1function in humans is controversial. RCAS1 overexpression leads to the generation of theTn glycan antigen (N-acetyl-D-galactosamine, GalNAc) recognized by the 22-1-1monoclonal antibody. The objective of this study is to examineTn glycan antigen function in colorectal cancer and to determine its relationship to CD8 + Tcells and prognosis. . Using Cox multivariate analysis and the Kaplan-Meier method,Tn and CD8 positivity were determined to be mutually independent prognostic factors (P = 0.0266 and 0.0210, respectively).Tn + patients with CD8 + TILs exhibited better survival thanTn + /CD8 À patients (P = 0.0129). For CD8 À patients,Tn positivity was associated with decreased survival from that seen in Tn À patients (P = 0.0097), suggesting that Tn exerts a function independent of CD8 + T cells in tumor progression. In all patients and cases with synchronous liver metastases (n = 29), theTn + /CD8À survival rate was significantly lower than that seen for other groups (P = 0.0001 and 0.0063, respectively). The average number of liver metastases in Tn + /CD8 À cases also increased (mean, 8.2 tumors; P = 0.0032). Multivariate analysis identified Tn + /CD8À status and Dukes' staging as independent prognostic factors (P = 0.0016 and <0.0001, respectively).Conclusions: Tn may encourage invasion and innidiation through a mechanism independent of CD8 + Tcells.Thus,Tn + /CD8 À status is a risk factor for multiple liver metastases development and an independent negative prognostic factor for colorectal cancer.

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Section: Discussionsupporting

confidence: 69%

“…In contrast, Okada et al reported that the proportion of apoptotic CD8 + TILs was significantly higher in RCAS1-positive colorectal cancer samples than in RCAS1-negative tumors (24). Their data suggest that the prognostic value of the presence of TILs, including CD8 + T cells, depends on RCAS1 expression.…”

Section: Discussionmentioning

confidence: 57%

Tumor-Associated Antigen Recognized by the 22-1-1 Monoclonal Antibody Encourages Colorectal Cancer Progression under the Scanty CD8+ T Cells

Oshikiri¹,

Miyamoto²,

Morita³

et al. 2006

Clinical Cancer Research

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“…RCAS1 is a type II membrane protein and expressed on several kinds of carcinomas (57,58). In vitro studies of RCAS1 indicated that it might act as an apoptosis-inducing factor, since RCAS1 induced apoptosis in its receptor expressing cells, such as T, B and NK cells (56).…”

Section: Introductionmentioning

confidence: 99%

CD44v6, MMP-7 and nuclear Cdx2 are significant biomarkers for prediction of lymph node metastasis in primary gastric cancer

Okayama

Kumamoto²,

Saitou³

et al. 2009

Oncol Rep

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Abstract. The aim of this study was to examine the expression of CD44v6, CD54, Cdx2, CXCL5, Cyclin B1, MMP-7, nm23, RCAS1 and Survivin in primary gastric cancer and to investigate whether these molecules were useful in predicting the lymph node status. They were selected as candidates for indicators of lymph node metastasis from various kinds of cancer-associated genes reported previously. In 135 cases of radically resected primary gastric adenocarcinoma, we investigated the association between the expression of these molecules and clinocopathologic factors by immunohistochemistry. The results revealed that the expression of CD44v6 and MMP-7 were significantly associated with lymph node status. By contrast, nuclear Cdx2 expression was found to be inversely correlated with lymph node metastasis. Moreover, multivariate analysis demonstrated that CD44v6, MMP-7 and nuclear Cdx2 were independent predictors for lymph node status. In conclusion, our results suggest that positive expression of both CD44v6 and MMP-7, and negative expression of nuclear Cdx2 may serve as powerful predictors of lymph node metastasis in gastric cancer. Combined evaluation of these markers could be further useful to predict lymph node status clinically.

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“…1 Immunohistochemical studies with tissue samples collected from cancer patients revealed that RCAS1 expression is associated with the number of apoptotic lymphocytes surrounding tumors. [2][3][4][5][6] In addition, RCAS1 expression has been correlated significantly with poor overall survival in patients with several malignancies. [7][8][9][10][11][12][13][14] RCAS1 expression also has been related to aggressive characteristics of cancer, such as the invasive potential of uterine cervical cancer and tumor size in gastric and uterine cancer.…”

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confidence: 99%

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

Sonoda

Miyamoto

Yamazaki

et al. 2007

Cancer

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BACKGROUND.The expression of receptor‐binding cancer antigen expressed on SiSo cells (RCAS1) is related significantly to the overall survival of patients with various cancers. RCAS1 reportedly induces apoptotic cell death in peripheral lymphocytes, which may contribute to the escape of tumor cells from immune surveillance. RCAS1 expression also has been related to tumor invasiveness and size in uterine cervical cancer. To clarify whether RCAS1 exacerbates tumor progression, the authors investigated the association between RCAS1 expression and tumor growth potential.METHODS.The authors constructed small interfering ribonucleic acid (RNA) (siRNA) to target RCAS1. After transfection of siRNA and the RCAS1‐encoding gene, growth of tumor cells was assessed in vitro and in vivo. The correlation between RCAS1 expression and angiogenesis was investigated in the transfected cells and in inoculated tumors from nude mice. In addition, the same association was investigated immunohistochemically with tissue samples from patients with uterine cervical cancer.RESULTS.Knockdown of RCAS1 expression by siRNA significantly suppressed the in vivo growth of SiSo and HOUA tumor cells (P < .005); however, in vitro cell growth was not affected significantly. Enhanced RCAS1 expression significantly promoted in vivo growth, but not in vitro growth, of tumors derived from COS‐7 cells (P = .0039). Introduction of the RCAS1‐encoding gene increased expression of vascular endothelial growth factor (VEGF). In uterine cervical cancer, RCAS1 expression was associated significantly with VEGF expression (P = .0407) and with microvessel density (P = .0108).CONCLUSIONS.RCAS1 may be a pivotal regulator of tumor growth through angiogenesis. Continued exploration of the biologic function of RCAS1 may allow the development of novel therapeutic strategies for uterine cancer. Cancer 2007. © 2007 American Cancer Society.

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Expression of Tumor-Associated Membrane Antigen, RCAS1, in Human Colorectal Carcinomas and Possible Role in Apoptosis of Tumor-Infiltrating Lymphocytes

Cited by 25 publications

References 29 publications

Tumor-Associated Antigen Recognized by the 22-1-1 Monoclonal Antibody Encourages Colorectal Cancer Progression under the Scanty CD8+ T Cells

Tumor-Associated Antigen Recognized by the 22-1-1 Monoclonal Antibody Encourages Colorectal Cancer Progression under the Scanty CD8+ T Cells

CD44v6, MMP-7 and nuclear Cdx2 are significant biomarkers for prediction of lymph node metastasis in primary gastric cancer

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

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