Lewis lung carcinoma progression is facilitated by TIG-3 fibroblast cells

Yoshikane Yamauchi, Yotaro Izumi, Keisuke Asakura, Kenji Kawai, Masatoshi Wakui, Mitsuyo Ohmura, Makoto Suematsu, Hiroaki Nomori

Research output: Contribution to journalArticle

1 Citation (Scopus)

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. Materials and 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 coimplantation 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 coimplantation, 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)3791-3798
Number of pages8
JournalAnticancer research
Volume33
Issue number9
Publication statusPublished - 2013 Sep 1

Keywords

  • Fibroblast
  • Invasion
  • LLC cells
  • Lung cancer
  • TGF-beta
  • TIG-3

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Lewis lung carcinoma progression is facilitated by TIG-3 fibroblast cells'. Together they form a unique fingerprint.

  • Cite this

    Yamauchi, Y., Izumi, Y., Asakura, K., Kawai, K., Wakui, M., Ohmura, M., Suematsu, M., & Nomori, H. (2013). Lewis lung carcinoma progression is facilitated by TIG-3 fibroblast cells. Anticancer research, 33(9), 3791-3798.