Abstract
Abstract Lung cancer is the most common cause of cancer deaths worldwide. 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, and identified a secreted protein, LASEP1 (lung cancer-associated serum protein 1). Immunohistochemical staining using tumor tissue microarrays consisting of 374 non-small cell lung cancers (NSCLCs) confirmed that LASEP1 protein was frequently over-expressed in various histological types of lung cancers; positive staining of LASEP1 was observed in 210 (56.1%) of 374 NSCLCs, while it was observed in 9 (69.2%) of 13 small cell lung cancers (SCLCs). In addition, a high level of LASEP1 expression was associated with poor prognosis for patients with NSCLC (P<0.0001 by log-rank test). Multivariate analysis confirmed its independent prognostic value (P<0.0001 by log-rank test). Serum LASEP1 levels were higher in NSCLC as well as SCLC 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, whereas induction of exogenous expression of LASEP1 conferred growth-promoting activity and enhanced the cell mobility in vitro. We found a LASEP1 receptor (LASEPR) which interacts with LASEP1 on lung cancer cell surface. Suppression of LASEPR expression by siRNAs inhibited the growth of cancer cells. LASEP1-LASEPR interaction promoted the cell growth in an anticrime/paracrine manner. LASEP1 is a potential target for the development of diagnostic and prognostic biomarkers as well as therapeutic drugs for lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3040. doi:10.1158/1538-7445.AM2011-3040
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