An Explore Study on the Expression of Small Cell Lung Cancer-related Antigens in Lung Adenocarcinoma Stem cells

Abstract: Cancer stem cells (CSC) represent a subtype of undifferentiated cells that have the ability to self-renew. It has been recognized that for the CSC of lung adenocarcinoma， the regulatory mechanisms of self-renewal are identical to the embryonic stem cells， that is， they over-express OCT4， Nanog and Sox2 pluripotent genes. However， the phenotypic characteristics of these malignant stem cells remained disputes currently. With the sphere-forming assay， we herein enriched the CSC from SPC-A1 cell line and thereby， analyzed their molecular phenotypes. Our results indicated that these pulmospheres co-expressed multiple lineage markers of the proximal and distal respiratory epithelium in the lung， such as the ciliated columnar cell marker Foxj1， the non-ciliated columnar (Clara) cell marker CCSP， the pulmonary neuroendocrine cell marker GRP， the type II alveolar cell marker SP-C and its transcription factor TTF-1. These pulmospheres were also recognized by three monoclonal antibodies specific for small cell lung cancer (2F7， 4B3 and E6). By using of gene silencing technique that specially depleted the expression of OCT4 in these cells， the all above-mentioned markers (expect E6) were disappeared. These data demonstrated that the CSC in lung adenocarcinoma shared molecular phenotypes with the pluripotent progenitor cells of respiratory epithelium in human lung. Moreover， our preliminary studies showed that the Hirsutella Hepialid of Cordyceps Sinensis， a traditional Chinese medicine， contained some ingredients with anti-cancer activities. These ingredients were able to potentially inhibit the proliferation of pulmospheres in vitro. These results point out that the isolation and characterization of these anti-cancer activities will provide a novel direction for the development of CSC-targeted drugs against lung cancer.

CSTR: 32200.14.cjcb.2013.12.0003