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Publication : Interference with the complement system by tumor cell membrane type-1 matrix metalloproteinase plays a significant role in promoting metastasis in mice.

First Author  Rozanov DV Year  2006
Journal  Cancer Res Volume  66
Issue  12 Pages  6258-63
PubMed ID  16778201 Mgi Jnum  J:110103
Mgi Id  MGI:3639370 Doi  10.1158/0008-5472.CAN-06-0539
Citation  Rozanov DV, et al. (2006) Interference with the complement system by tumor cell membrane type-1 matrix metalloproteinase plays a significant role in promoting metastasis in mice. Cancer Res 66(12):6258-63
abstractText  Neoplasms have developed strategies to protect themselves against the complement-mediated host immunity. Invasion- and metastasis-promoting membrane type-1 (MT1) matrix metalloproteinase (MMP) is strongly associated with many metastatic cancer types. The relative importance of the individual functions of MT1-MMP in metastasis was, however, unknown. We have now determined that the expression of murine MT1-MMP in murine melanoma B16F1 cells strongly increased the number of metastatic loci in the lungs of syngeneic C57BL/6 mice. In contrast, MT1-MMP did not affect the number of metastatic loci in complement-deficient C57BL/6-C3-/- mice. Our results indicated, for the first time, that the anticomplement activity of MT1-MMP played a significant role in promoting metastasis in vivo and determined the relative importance of the anticomplement activity in the total metastatic effect of this multifunctional proteolytic enzyme. We believe that our results shed additional light on the functions of MT1-MMP in cancer and clearly make this protease a promising drug target in metastatic malignancies.
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