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

First Author  Jost M Year  2006
Journal  Cancer Res Volume  66
Issue  10 Pages  5234-41
PubMed ID  16707448 Mgi Jnum  J:109057
Mgi Id  MGI:3625654 Doi  10.1158/0008-5472.CAN-05-4315
Citation  Jost M, et al. (2006) Earlier onset of tumoral angiogenesis in matrix metalloproteinase-19-deficient mice. Cancer Res 66(10):5234-41
abstractText  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.
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