We examined the biologic properties of a small-cell-lungcarcinoma (SCLC) cell line (designated MN-I I 12) established from a patient with SCLC who showed paraneoplastic retinopathy syndrome. Morphologic and immunocytochemical analyses showed that MN-I I I2 cells possess features of the classic type of SCLC. MN-I I I 2 cells grew in suspension forming relatively large clumps of cells with a doubling time of 72 hr. By light-microscope examination, the cells were relatively small and had scanty cytoplasm. The cells produced NSE, ACTH and CK (BB isozyme); they also expressed recoverin, a novel photoreceptor protein, detected by Northern-blot and Westernimmunoblot analysis using human-recoverin-specific DNA probe and anti-bovine-recoverin polyclonal antibody. This report shows that human recoverin is expressed in cultured SCLC cells. Our results support the hypothesis that, in cancer-associated retinopathy (CAR) patients, auto-immune antibody targeting for ectopic recoverin in SCLC is initially produced and cross-reacts with the retinal protein, resulting in the retinal degeneration that occurs in CAR patients.o 1996 Wiley-Liss, Inc.Small-cell lung carcinoma (SCLC) occurs in approximately 15% of total lung carcinoma, which has become the most common cause of cancer deaths among Japanese men. SCLC may originate from the Kultschitzky cells lining the bronchial mucosa and possess characteristics of the APUD series of neuro-endocrine cells. They express neuronal differentiation antigens, including NSE, the BB isozyme of CK, receptors for nerve growth factor, and acetylcholine (Greco et al., 1981). Compared with non-SCLCs, they are more frequently associated with paraneoplastic neuropathy syndromes (PNS), such as Eaton-Lambert myasthenic syndrome (ELMS) and paraneoplastic encephalomyelitis/sensory neuropathy syndrome (PEM/ SNS), which are caused by remote effects of cancer (O'Neill et aL, 1988;Dalmau et al., 1992). The neuronal characteristics of SCLC may provide the antigenic stimulus required for production of a cross-reacting immune response (Kornguth, 1989). Cancer-associated retinopathy (CAR) syndrome is one of such syndromes, and is characterized by degenerative retina without evidence of severe inflammatory processes or metastasis or any known direct effect of the cancer cells (Thirkill et al., 1989). A high percentage of patients reveal a characteristic antibody, which recognizes a 23-kDa antigen (Thirkill et al., 1993). Recoverin, a photoreceptor-specific protein, has been determined as a candidate for the 23-kDa CAR antigen which was screened in human retinal cDNA library using autoantibodies from a CAR patient (Thirkill et al., 1992). According to the auto-immune hypothesis that has been proposed, the process arises as a reaction to the 23-kDa antigen shared by SCLC and the retina; however, such CAR antigen has not yet been clarified in SCLC cells (Thirkill et al., 1989(Thirkill et al., , 1993. In previous studies, however, these cells were usually derived from a tumor of patients without CAR (Thirkill et al.,...