title: Spheroid culture of primary lung cancer cells with neuregulin 1/HER3 pathway activation.
abstract: BACKGROUND
  Primary culture of cancer cells is expected to be useful for investigating the biology of cancer and predicting chemosensitivity for individual patients, yet has been hampered by technical difficulties. We recently developed the cancer tissue-originated spheroid (CTOS) method for the primary culture of colorectal cancer cells. In the present study, we applied this system to the primary culture of non-small-cell lung cancer.
  
  
  METHODS
  We used 125 surgical specimens and 18 pleural effusions for CTOS preparation. Partially digested tumor fragments were cultured in a medium for embryonic stem cells. CTOSs were subjected to sensitivity assay and signal transduction assay for the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib. We also investigated the effects of growth factors in culturing lung cancer CTOS.
  
  
  RESULTS
  The success rate of CTOS preparation from surgical specimens was 80.0%. The CTOS method was also suitable for culturing tumor spheroids from pleural effusions. CTOSs from lung cancer consisted mostly of pure cancer cells. CTOSs and CTOS-derived xenografts retained the characteristics of the original tumors. In vitro assay results showed that EGFR mutation status and expression levels corresponded with erlotinib sensitivity, confirming previous clinical findings. Furthermore, we found that neuregulin 1, a ligand of HER3, potently induced CTOS growth.
  
  
  CONCLUSIONS
  The CTOS method enables us to obtain primary lung tumor cells of high viability and purity. CTOS could be a new platform for studying lung cancer biology.
authors: Departments of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors: Hiroko
authors: H
authors: Endo
authors: Jiro
authors: J
authors: Okami
authors: Hiroaki
authors: H
authors: Okuyama
authors: Toru
authors: T
authors: Kumagai
authors: Junji
authors: J
authors: Uchida
authors: Jumpei
authors: J
authors: Kondo
authors: Tetsuo
authors: T
authors: Takehara
authors: Yasuko
authors: Y
authors: Nishizawa
authors: Fumio
authors: F
authors: Imamura
authors: Masahiko
authors: M
authors: Higashiyama
authors: Masahiro
authors: M
authors: Inoue
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009154:Mutation / Q000235:genetics; D020890:Neuregulin-1 / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D020893:Receptor, ErbB-3 / Q000378:metabolism*; D015398:Signal Transduction; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C094131:NRG1 protein, human; D020890:Neuregulin-1; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; C581292:ERBB3 protein, human; D066246:ErbB Receptors; D020893:Receptor, ErbB-3