Earlier onset of tumoral angiogenesis in matrix metalloproteinase-19-deficient mice.

Abstract

Among matrix metalloproteinases (MMP), MMP-19 displays unique structural features and tissue distribution. In contrast to most MMPs, MMP-19 is expressed in normal human epidermis and down-regulated during malignant transformation and dedifferentiation. The contribution of MMP-19 during tumor angiogenesis is presently unknown. In an attempt to give new insights into MMP-19 in vivo functions, angiogenic response of mutant mice lacking MMP-19 was analyzed after transplantation of murine malignant PDVA keratinocytes and after injection of Matrigel supplemented with basic fibroblast growth factor. In situ hybridization and immunohistochemical analysis revealed that MMP-19 is produced by host mesenchymal cells but not by endothelial capillary cells or CD11b-positive inflammatory cells. Based on a new computer-assisted method of quantification, we provide evidence that host MMP-19 deficiency was associated with an increased early angiogenic response. In addition, increased tumor invasion was observed in MMP-19-/- mice. We conclude that, in contrast to most MMPs that promote tumor progression, MMP-19 is a negative regulator of early steps of tumor angiogenesis and invasion. These data highlight the requirement to understand the individual functions of each MMP to improve anticancer strategies.

• Authors: Maud Jost, Alicia R Folgueras, Françoise Frérart, Alberto M Pendas, Silvia Blacher, Xavier Houard, Sarah Berndt, Carine Munaut, Didier Cataldo, Jesus Alvarez, Laurence Melen-Lamalle, Jean-Michel Foidart, Carlos López-Otín, Agnès Noël
• Journal: Cancer research (Cancer Res) Vol. 66 Issue 10 Pg. 5234-41 (May 15 2006) ISSN: 0008-5472 [Print] United States
• PMID: 16707448 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Drug Combinations
• Laminin
• Proteoglycans
• matrigel
• Collagen
• Matrix Metalloproteinases, Secreted
• Metalloendopeptidases
• matrix metalloproteinase 19

Topics

• Animals
• Collagen
• Drug Combinations
• Female
• Laminin
• Male
• Matrix Metalloproteinases, Secreted
• Metalloendopeptidases (biosynthesis, deficiency, genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Neoplasm Invasiveness
• Neovascularization, Pathologic (enzymology, pathology)
• Proteoglycans
• Skin Neoplasms (blood supply, enzymology, pathology)
• Stromal Cells (enzymology)