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

Dmitri Rozanov, Alexei Y. Savinov, Vladislav S. Golubkov, Stephen Tomlinson, Alex Y. Strongin

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6258-6263
Number of pages6
JournalCancer Research
Volume66
Issue number12
DOIs
StatePublished - Jun 15 2006
Externally publishedYes

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Matrix Metalloproteinase 14
Cell Membrane
Neoplasm Metastasis
Neoplasms
Peptide Hydrolases
Multifunctional Enzymes
Inbred C57BL Mouse
Immunity
Melanoma
Lung
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Interference with the complement system by tumor cell membrane type-1 matrix metalloproteinase plays a significant role in promoting metastasis in mice. / Rozanov, Dmitri; Savinov, Alexei Y.; Golubkov, Vladislav S.; Tomlinson, Stephen; Strongin, Alex Y.

In: Cancer Research, Vol. 66, No. 12, 15.06.2006, p. 6258-6263.

Research output: Contribution to journalArticle

Rozanov, Dmitri ; Savinov, Alexei Y. ; Golubkov, Vladislav S. ; Tomlinson, Stephen ; Strongin, Alex Y. / Interference with the complement system by tumor cell membrane type-1 matrix metalloproteinase plays a significant role in promoting metastasis in mice. In: Cancer Research. 2006 ; Vol. 66, No. 12. pp. 6258-6263.
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