Nakashima M, Sonoda K, Watanabe T
Department of Molecular Immunology, Medical Institute of Bioregulation, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Nat Med. 1999 Aug;5(8):938-42. doi: 10.1038/11383.
Tumor-associated antigens that can be recognized by the immune system include the MAGE-family, p53, MUC-1, HER2/neu and p21ras. 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 surfaces. Tumor cells may also evade immune attack by expressing CD95 (APO-1/Fas) ligand or other molecules that induce apoptosis in activated T cells. 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.
可被免疫系统识别的肿瘤相关抗原包括MAGE家族、p53、MUC-1、HER2/neu和p21ras。尽管肿瘤细胞表达这些独特的抗原，但免疫系统对肿瘤的清除往往效率低下。推测的机制包括肿瘤细胞共刺激分子或黏附分子表达不足，或其细胞表面抗原加工和呈递存在缺陷。肿瘤细胞还可能通过表达CD95（APO-1/Fas）配体或其他诱导活化T细胞凋亡的分子来逃避免疫攻击。在此，我们描述了RCAS1（在SiSo细胞上表达的受体结合癌抗原），一种在人类癌细胞上表达的膜分子。RCAS1作为一种配体，作用于存在于各种人类细胞系以及正常外周淋巴细胞（如T细胞、B细胞和NK细胞）上的一种假定受体。淋巴细胞活化可增强该受体的表达。RCAS1抑制表达受体细胞的体外生长并诱导凋亡性细胞死亡。鉴于这些结果，肿瘤细胞可能通过表达RCAS1来逃避免疫监视，RCAS1会抑制克隆扩增并诱导RCAS1受体阳性免疫细胞凋亡。
