HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

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.
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
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)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: