Interference with the complement system by tumor cell membrane type-1 matrix metalloproteinase plays a significant role in promoting metastasis in mice.
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.
Rozanov
Dmitri V
DV
Cell Adhesion and Extracellular Matrix Biology, Burnham Institute for Medical Research, La Jolla, California 92037, USA.
Savinov
Alexei Y
AY
Golubkov
Vladislav S
VS
Tomlinson
Stephen
S
Strongin
Alex Y
AY
D000818:Animals; D003176:Complement C3 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D003169:Complement Inactivator Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005354:Fibrosarcoma / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000276:immunology / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D053511:Matrix Metalloproteinase 14; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D053504:Matrix Metalloproteinases, Membrane-Associated; D008546:Melanoma, Experimental / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000201:enzymology* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D014162:Transfection
D003176:Complement C3; D003169:Complement Inactivator Proteins; C507096:Mmp14 protein, mouse; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D053511:Matrix Metalloproteinase 14