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Inhibition of cell growth and induction of apoptotic cell death by the human tumor-associated antigen RCAS1

Nature Medicine volume 5, pages 938–942 (1999)Cite this article

Abstract

Tumor-associated antigens that can be recognized by the immune system include the MAGE-family, p53, MUC-1, HER2/neu and p21ras (refs. 1, 2, 3, 4, 5, 6). Despite their expression of these distinct antigens, tumor elimination by the immune system is often inefficient. Postulated mechanisms include insufficient expression of co-stimulatory or adhesion molecules by tumor cells, or defective processing and presentation of antigens on their cell surfaces7,8,9,10. Tumor cells may also evade immune attack by expressing CD95 (APO-1/Fas) ligand or other molecules that induce apoptosis in activated T cells11,12,13. Here we describe RCAS1 (receptor-binding cancer antigen expressed on SiSo cells), a membrane molecule expressed on human cancer cells. RCAS1 acts as a ligand for a putative receptor present on various human cell lines and normal peripheral lymphocytes such as T, B and NK cells. The receptor expression was enhanced by activation of the lymphocytes. RCAS1 inhibited the in vitro growth of receptor-expressing cells and induced apoptotic cell death. Given these results, tumor cells may evade immune surveillance by expression of RCAS1, which would suppress clonal expansion and induce apoptosis in RCAS1 receptor-positive immune cells.

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Figure 1: Structure of RCAS1 and induction of cell cycle arrest and apoptotic cell death in receptor-positive K562 cells.
Figure 2: Inhibition of cell growth and induction of apoptosis in K562 by inducible expression of RCAS1 antigen.
Figure 3: Expression and function of RCAS1 receptor on normal PBLs cultured with or without IL-2.

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Acknowledgements

We thank P.D. Burrows and T.H. Bester for their critical reading and comments. We also thank H. Katsuta for his help. The work is supported by the Grant-in-Aid for Cancer Reserch from The Ministry of Education, Science and Culture of Japan (Grant number: 10153245).

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Authors and Affiliations

  1. Department of Molecular Immunology, Medical Institute of Bioregulation, 3-1-1 Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan

    Manabu Nakashima & Takeshi Watanabe

  2. Department of Gynecology and Obstetrics, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan

    Kenzo Sonoda

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  1. Manabu Nakashima
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Correspondence to Takeshi Watanabe.

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Nakashima, M., Sonoda, K. & 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). https://doi.org/10.1038/11383

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