Abstract 3005: Characterization of a lung cancer growth factor, LASEP1 as a serological and prognostic biomarker and a therapeutic target

Abstract

Abstract To identify molecules that might serve as biomarkers or targets for the development of novel molecular therapies, we have been screening genes encoding transmembrane/secretory proteins that are up-regulated in lung cancers, using cDNA microarrays. During this process, we identified a secreted protein, LASEP1 (lung cancer-associated serum protein 1) as a candidate. Immunohistochemical staining using tumor tissue microarrays consisting of 374 non-small cell lung cancers (NSCLC) revealed that LASEP1 protein was frequently over-expressed in lung cancers; positive staining of LASEP1 was observed in 210 (56.1%) of 374 NSCLC, while that was observed in 9 (69.2%) of 13 small cell lung cancers (SCLC). In addition, a strong LASEP1 positivity was associated with poor prognosis for patients with NSCLC (P<0.001 by log-rank test), and multivariate analysis confirmed its independent prognostic value. Serum LASEP1 levels were higher in NSCLCs as well as SCLCs patients than in healthy volunteers. The proportion of serum LASEP1-positive cases was 127 (38.6%) of 329 lung cancers, while 4 (3.9%) of 102 healthy volunteers were falsely diagnosed. Furthermore, treatment of lung cancer cells with siRNAs against LASEP1 suppressed its expression and resulted in growth suppression of the lung cancer cells; on the other hand, induction of exogenous expression of LASEP1 conferred growth-promoting activity and enhanced the cell mobility in vitro. Interestingly, the growth activity of the LASEP1-positive cells was neutralized by addition of originally developed anti-LASEP1 monoclonal antibodies into their culture media. The systemic administration of the anti-LASEP1 antibody to LASEP1-positive tumor-implanted mice significantly suppressed tumor growth without any adverse events. We found a receptor (LASEPR) which interacts with LASEP1 on lung cancer cell surface and is essential for the growth of cancer cells. The data suggest that the LASEP1-LASEPR interaction could promote the cancer cell growth in an autocrine manner. LASEP1 is a potential serological and prognostic biomarker and a therapeutic target for lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3005. doi:1538-7445.AM2012-3005