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

Abstract

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.

• Authors: Yasusei 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
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 287 Issue 46 Pg. 38716-28 (Nov 09 2012) ISSN: 1083-351X [Electronic] United States
• PMID: 22992737 (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

Topics

• 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)