Abstract 519: V-set and immunoglobulin domain containing 1 (VSIG1) demonstrates a tumor suppressive function in gastric cancer and non-small cell lung cancer (2015)

Abstract V-set and immunoglobulin domain containing 1 (VSIG1) was recently identified as a novel member of immunoglobulin-like cell-adhesion molecules. In human, VSIG1 has 2 transcript variant forms (variant 1 and variant 2). In normal tissues, VSIG1 was reported to be expressed predominantly in stomach and testis. In cancerous tissues, the expression of VSIG1 was shown to be restricted in a part of gastric, esophageal, and ovarian cancers. However, the role of VSIG1 in cancer progression has not been elucidated. VSIG1 protein expression in human normal tissues obtained at autopsy was detected by western blot analysis. We also analyzed VSIG1 protein expression in 8 non-small cell lung cancer (NSCLC) cell lines and 8 gastric cancer (GC) cell lines by western blot. Relative mRNA expression was evaluated by quantitative real-time PCR in patients with resected NSCLC (n = 69). Protein expression in NSCLC (n = 277) and GC (n = 362) were analyzed using immunohistochemistry. The effects of VSIG1 in proliferation, migration, and invasion were assessed in NSCLC and GC cell lines by ectopic expression of a human full-length VSIG1 variant 2 cDNA or application of specific VSIG1 siRNA. In normal tissues of 15 organs (brain, heart, lung, esophagus, stomach, intestine, colon, rectum, liver, spleen, pancreas, adrenal gland, kidney, testis, and ovary), VSIG1 protein expression was detected in only stomach and testis, and variant 2 mRNA expression level was significantly higher than variant 1 in both stomach and testis (p&amp;lt;0.00001). VSIG1 mRNA was overexpressed in 21 NSCLC patients (30.4% of patients), in whom variant 2 mRNA expression level was higher than variant 1 in 15 patients (71.4%). VSIG1 protein expression was detected in 7.2% of NSCLC and 39.5% of GC. In NSCLC, VSIG1 protein expression was restricted in adenocarcinoma histology (p = 0.0002) and was negatively correlated with TTF-1 protein expression (p = 0.002). In GC, patients with VSIG1 decreased expression tumors had a worse overall rate of survival than those with expressing tumors (p = 0.014, log-rank test). In NSCLC, however, VSIG1 protein expression level did not have significant prognostic impact. In 16 NSCLC and GC cell lines, VSIG1 protein expression was detected in only MKN45 cells. Overexpression of VSIG1 significantly reduced proliferation and migration in H1299, MKN1, and MKN28 cells, and also inhibited invasion in MKN1 and MKN28 cells. On the other hand, VSIG1 downregulation enhanced proliferation in MKN45 cells. From these findings, we conclude that VSIG1 has a tumor suppressive function which contributes to a less proliferative and invasive phenotype in cancer cells. We are exploring to identify the binding partners of VSIG1 using LC-MS/MS analysis. The results will be shown and discussed. Citation Format: Yusuke Inoue, Nobuya Kurabe, Shun Matsuura, Matsuyoshi Maeda, Tomoaki Kahyo, Hisaki Igarashi, Kazuhito Funai, Hiroshi Niwa, Hiroshi Ogawa, Kazuya Shinmura, Hiroyuki Konno, Takafumi Suda, Haruhiko Sugimura. V-set and immunoglobulin domain containing 1 (VSIG1) demonstrates a tumor suppressive function in gastric cancer and non-small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 519. doi:10.1158/1538-7445.AM2015-519