title: Involvement of intermediate filament nestin in cell growth of small-cell lung cancer.
abstract: BACKGROUND
  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 is involved in malignant processes. This study investigated the expression and function of nestin in small-cell lung cancer (SCLC).
  
  
  METHODS
  Expression of nestin and achaete-scute homolog 1 (ASH1) was studied in 21 lung cancer cell lines. To assess the function of nestin, a short hairpin RNA (shRNA) targeting nestin was transfected into two SCLC cell lines (DMS53 and SBC3), and cloned cells that showed apparent down-regulation of nestin were obtained. Nestin expression was also studied immunohistochemically in surgically resected SCLC primary tumors and metastatic SCLC tumors obtained from autopsy cases.
  
  
  RESULTS
  Nestin was expressed in nine of 10 SCLC cell lines. The nestin expression level was significantly higher in SCLC cell lines than in 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. Nestin knock-down cells created by transfection with shRNA exhibited decreased invasion and cell proliferation capabilities. Furthermore, nestin was detected in SCLC tumor cells and tumor vessels in all clinical tumor specimens.
  
  
  CONCLUSIONS
  Nestin is expressed in SCLC in association with neuroendocrine features and participates in malignant phenotypes, including cell growth. Therefore, nestin may be a novel therapeutic target for SCLC.
authors.affiliation: Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Takakuwa
authors.forename: Ken
authors.initials: K
authors.lastname: Maeno
authors.forename: Eiji
authors.initials: E
authors.lastname: Kunii
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ozasa
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Hijikata
authors.forename: Takehiro
authors.initials: T
authors.lastname: Uemura
authors.forename: Daishi
authors.initials: D
authors.lastname: Kasai
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Ohkubo
authors.forename: Mikinori
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Oguri
authors.forename: Akio
authors.initials: A
authors.lastname: Niimi
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D015536:Down-Regulation; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D064231:Nestin / Q000235:genetics / Q000378:metabolism*; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D007381:Intermediate Filament Proteins; D064231:Nestin; C065500:ASCL1 protein, human
keywords: Achaete-scute homolog 1; Intermediate filament; Nestin; Neuroendocrine tumor; Short-hairpin RNA; Small cell lung cancer