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. |