Matrix metalloproteinase-13 (MMP-13) directly and indirectly promotes tumor angiogenesis.

Matrix metalloproteinases (MMPs) are extracellular zinc-dependent endopeptidases involved in the degradation and remodeling of extracellular matrix in physiological and pathological processes. MMPs also have a role in cell proliferation, migration, differentiation, angiogenesis, and apoptosis. We previously identified cancer invasion-related factors by comparing the gene expression profiles between parent and the highly invasive clone of cancer cells. Matrix metalloproteinase-13 (MMP-13) was identified as a common up-regulated gene by cancer invasion-related factors. Although MMP-13 slightly promoted tumor invasion, we found that MMP-13 was involved in tumor angiogenesis. Conditioned medium from MMP-13-overexpressing cells promoted capillary formation of immortalized human umbilical vein endothelial cells. Furthermore, treatment with recombinant MMP-13 protein enhanced capillary tube formation both in vitro and in vivo. MMP-13-promoted capillary tube formation was mediated by activation of focal adhesion kinase and ERK. Interestingly, MMP-13 promoted the secretion of VEGF-A from fibroblasts and endothelial cells. By immunohistochemical analysis, we found a possible correlation between MMP-13 expression and the number of blood vessels in human cancer cases. In summary, these findings suggest that MMP-13 may directly and indirectly promote tumor angiogenesis.
AuthorsYasusei Kudo, Shinji Iizuka, Maki Yoshida, Takaaki Tsunematsu, Tomoyuki Kondo, Ajiravudh Subarnbhesaj, Elsayed M Deraz, Samadarani B S M Siriwardena, Hidetoshi Tahara, Naozumi Ishimaru, Ikuko Ogawa, Takashi Takata
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 287 Issue 46 Pg. 38716-28 (Nov 9 2012) ISSN: 1083-351X [Electronic] United States
PMID22992737 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • RNA, Small Interfering
  • Recombinant Proteins
  • Vascular Endothelial Growth Factor A
  • Matrix Metalloproteinase 13
  • Animals
  • Cell Line, Tumor
  • Fibroblasts (metabolism)
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms (drug therapy, metabolism)
  • Humans
  • Immunohistochemistry (methods)
  • Male
  • Matrix Metalloproteinase 13 (metabolism)
  • Neoplasm Metastasis
  • Neovascularization, Pathologic
  • Protein Structure, Tertiary
  • RNA, Small Interfering (metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins (chemistry)
  • Vascular Endothelial Growth Factor A (metabolism)

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