Abstract 4360: Involvement of intermediate filament nestin in cell growth of small-cell lung cancer.

Abstract

Abstract Small-cell lung cancer (SCLC) represents 13% of all newly diagnosed cases of lung cancer. Clinical progression of SCLC is rapid and aggressive. Unfortunately, 70% of SCLC cases have already metastasized at the time of diagnosis, and the recent median survival time and two-year survival rate in SCLC patients with extensive-stage disease is only 8-13 months and 5%, respectively. Clinical trials of SCLC treatments have been conducted since the mid-1980s, but have not achieved prolonged survival; this lack of success is likely due to a lack of appropriate target molecules. To improve outcomes for SCLC patients, new therapeutic strategies including novel molecular targets for SCLC are desired. Nestin is a class VI intermediate filament protein expressed in stem/progenitor cells during the development of the central nervous system. Nestin is detected in various types of tumors and reported to be involved in malignant phenotypes. Here, we investigated the expression and function of nestin in SCLC. At the beginning, protein expression of nestin and achaete-scute homolog 1 (ASH1) was studied in 21 lung cancer cell lines. Nestin was expressed in 9 of 10 SCLC cell lines. The nestin expression level in SCLC cell lines was significantly higher than that in non-small-cell lung cancer (NSCLC) cell lines (P<0.01). There was a statistically significant positive correlation between the expression levels of nestin and ASH1 in SCLC cell lines, but not in NSCLC cell lines. To assess the function of nestin, we transfected a short hairpin RNA (shRNA) targeting nestin into two SCLC cell lines, DMS53 and SBC3, and then obtained cloned cells that showed apparent down-regulation of nestin. Nestin knock-down cells created by transfection with shRNA exhibited decreased invasion and cell proliferation capabilities. In conclusion, Nestin is expressed in SCLC in association with neuro-endocrine feature and participates in malignant phenotypes including cell growth. Therefore, nestin may be a novel therapeutic target of SCLC. Additional in vivo study will be needed. Citation Format: Eiji Kunii, Osamu Takakuwa, Ken Maeno, Tetsuya Oguri, Midori Yokoyama, Hisatoshi Hijikata, Takehiro Uemura, Daishi Kasai, Hirotsugu Ohkubo, Mikinori Miyazaki, Akio Niimi. Involvement of intermediate filament nestin in cell growth of small-cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4360. doi:10.1158/1538-7445.AM2013-4360