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

Tumor-associated antigens that can be recognized by the immune system inclu de the MAGE-family, p53, MUC-1, HER2/neu and p21ras (refs. 1-6). Despite th eir expression of these distinct antigens, tumor elimination by the immune system is often inefficient. Postulated mechanisms include insufficient exp ression of co-stimulatory or adhesion molecules by tumor cells, or defectiv e processing and presentation of antigens on their cell surfaces(7-10) Tumo r 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 liga nd for a putative receptor present on various human cell lines and normal p eripheral lymphocytes such as T, B and NK cells. The receptor expression wa s enhanced by activation of the lymphocytes. RCAS1 inhibited the in vitro g rowth of receptor-expressing cells and induced apoptotic cell death. Given these results, tumor cells may evade immune surveillance by expression of R CAS1, which would suppress clonal expansion and induce apoptosis in RCAS1 r eceptor-positive immune cells.