title: Lewis lung carcinoma progression is facilitated by TIG-3 fibroblast cells.
abstract: BACKGROUND
  The interactions of tumor cells with stromal fibroblasts influence tumor biology, but the exact mechanisms involved are still unclear. In the present study, we evaluated the effects of a human lung fibroblast cell line, TIG-3, on Lewis lung carcinoma (LLC) cells both in vitro and in vivo.
  
  
  METHODS
  LLC and TIG-3 cells were co-cultured/co-implanted in vitro and in vivo. Cell invasion was assayed. Local tumor growth, as well as lung metastasis, were evaluated after subcutaneous cell co-implantation into NOD/SCID/γ-null (NOG) mice. LLC, and TIG-3 cells were pre-treated with either SB431542, a small molecule TGF-β receptor antagonist, or siRNA for transforming growth factor (TGF)-β before co-culture or co-implantation, and the effects of pre-treatments were compared both in cell culture and in mice.
  
  
  RESULTS
  Subcutaneous LLC tumor growth (L group) in NOG mice was significantly increased by co-implantation of TIG-3 cells (L+T group) at four weeks. The number of macroscopic lung metastases was also significantly increased in the L+T group in comparison to the L group. In vitro cell invasion was significantly increased in the L+T group in comparison to the L group. In vitro expression of phosphorylated-SMAD3 was significantly increased in the L+T group in comparison to the L group. Furthermore, pre-treatment with either SB431542 or siRNA for TGF-β reduced the invasiveness both in culture and in mice.
  
  
  CONCLUSIONS
  This study suggested that in vitro as well as in vivo progression of LLC was facilitated by co-culture/co-implantation with TIG-3 cells, and that this process was at least in part dependent on TGF-β-mediated interactions.
authors.affiliation: Division of General Thoracic Surgery, Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. yotaro2008@gmail.com.
authors.forename: Yoshikane
authors.initials: Y
authors.lastname: Yamauchi
authors.forename: Yotaro
authors.initials: Y
authors.lastname: Izumi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Asakura
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawai
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Wakui
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Ohmura
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nomori
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018827:Carcinoma, Lewis Lung / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D018450:Disease Progression; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016212:Transforming Growth Factor beta
keywords: LLC cells; Lung cancer; TGF-beta; TIG-3; fibroblast; invasion