Inhibition of cell growth and induction of apoptotic cell death by the human tumor-associated antigen RCAS1
Inhibition of cell growth and induction of apoptotic cell death by the human tumor-associated antigen RCAS1
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DOI：
10.1038/11383
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发表时间：
1999-08-01
期刊：
影响因子：
82.9
通讯作者：
Watanabe, T
中科院分区：
文献类型：
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作者：
Nakashima, M;Sonoda, K;Watanabe, T
可被免疫系统识别的肿瘤相关抗原包括mage家族、p53、muc1、HER2/neu和p21ras（参考文献）。1 - 6)。尽管它们表达了这些不同的抗原，但免疫系统消除肿瘤的效率往往很低。假设的机制包括肿瘤细胞共刺激或粘附分子的表达不足，或抗原在其细胞表面的加工和呈递缺陷（7-10）肿瘤细胞也可能通过表达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（11-13）。在这里，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作为一种假定受体的配体存在于各种人类细胞系和正常外周血淋巴细胞（如T、B和NK细胞）上。受体的表达通过激活淋巴细胞而增强。RCAS1抑制受体表达细胞的体外生长，诱导凋亡细胞死亡。因此，肿瘤细胞可能通过表达RCAS1来逃避免疫监视，从而抑制RCAS1受体阳性免疫细胞的克隆扩增并诱导细胞凋亡。
Tumor-associated antigens that can be recognized by the immune system include the MAGE-family, p53, MUC-1, HER2/neu and p21ras (refs. 1-6). 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 surfaces(7-10) Tumor cells may also evade immune attack by expressing CD95 (APO-1/Fas) ligand or other molecules that induce apoptosis in activated T cells(11-13). 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.