Induction of MMP-13 expression in bone-metastasizing cancer cells by type I collagen through integrin α1β1 and α2β1-p38 MAPK signaling

Soichiro Ibaragi, Tsuyoshi Shimo, Nur Mohammad Monsur Hassan, Sachiko Isowa, Naito Kurio, Hiroki Mandai, Shinichi Kodama, Akira Sasaki

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: Breast cancer cells frequently metastasize to the skeleton and produce and secrete proteinases, such as matrix metalloproteinase-13 (MMP-13), which promote destruction of the bone matrix. However, the mechanism of MMP-13 expression induced in areas of bone metastasis is unknown. Here, the interaction between tumors and type I collagen in bone metastasis was investigated. Materials and Methods: A mouse model of bone metastasis was prepared by inoculating mice with suspensions of cells of the human metastatic breast cancer cell line MDA-MB-231 via the left cardiac ventricle. MMP-13 expression was examined by immunohistochemical, Western blot, and real-time RT-PCR analyses. Results: MMP-13 expression was highly up-regulated in MDA-MB-231 cells, and attachment of these cells to type I collagen and the induction of MMP-13 were down-regulated by treatment with integrin α1, α2 or β1 neutralizing antibodies. The attachment of MDA-MB-231 cells to type I collagen induced the activation of focal adhesion kinase (FAK) and p38 mitogen-activated protein kinase (MAPK). Inhibition of FAK and p38 MAPK down-regulated type I collagen-induced MMP-13 expression. Conclusion: Our study indicates that metastatic breast cancer cells in the bone microenvironment attached to type I collagen, which stimulated integrins α1β1 and α2β1, via FAK and p38 MAPK pathways, to induce MMP13 expression and further osteolysis.

Original languageEnglish
Pages (from-to)1307-1313
Number of pages7
JournalAnticancer research
Volume31
Issue number4
Publication statusPublished - Apr 1 2011

Keywords

  • Bone metastasis
  • Integrin
  • MAPK
  • MMP-13
  • Type I collagen

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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