Neutrophil-derived serine proteinases enhance membrane type-1 matrix metalloproteinase-dependent tumor cell invasion

Peter Shamamian, Ben J.Z. Pocock, Jess D. Schwartz, Sara Monea, Neal Chuang, David Whiting, Stuart G. Marcus, Aubrey C. Galloway, Paolo Mignatti

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22 Scopus citations

Abstract

Background. Matrix metalloproteinase-2 degrades a variety of basement membrane components and is essential for tumor invasion. We have previously reported that membrane type-1 matrix metalloproteinase (MT1-MMP) cooperates with neutrophil-derived serine proteinases (NDPs; elastase, cathepsin G, protease-3) to activate matrix metalloproteinase-2. We therefore hypothesized that NDPs enhance tumor-cell invasion. Methods. Clones of human HT1080 fibrosarcoma cells transfected with MT1-MMP sense (HT-SE) or antisense CDNA (HT-AS) were used. These cells express either high (HT-SE) or extremely low levels (HT-AS) of MT1-MMP relative to nontransfected HT1080 cells (HT-WT). The cells were incubated in the presence or absence of purified NDP, with or without α1-antitrypsin or the MMP inhibitor batimastat. Cell invasion was measured with the use of Boyden chambers with polycarbonate membranes coated with a reconstituted extracellular matrix. Results. Under control conditions HT-WT and HT-SE cells were 4-fold more invasive than HT-AS cells. The addition of NDP increased HT-WT and HT-SE cell invasion 60% to 100% but had no effect on HT-AS cells, α1-antitrypsin or batimastat did not decrease the baseline invasiveness of HT-WT and HT-SE cells; however, they abrogated the stimulatory effect of NDP. Conclusions. HT1080 cell invasion depends on MT1- MMP expression. MT1-MMP overexpression does not increase invasiveness by itself NDPs increase invasion by MT1-MMP expressing cells by activating matrix metalloproteinase-2.

Original languageEnglish (US)
Pages (from-to)142-147
Number of pages6
JournalSurgery
Volume127
Issue number2
DOIs
StatePublished - Jan 1 2000

ASJC Scopus subject areas

  • Surgery

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    Shamamian, P., Pocock, B. J. Z., Schwartz, J. D., Monea, S., Chuang, N., Whiting, D., Marcus, S. G., Galloway, A. C., & Mignatti, P. (2000). Neutrophil-derived serine proteinases enhance membrane type-1 matrix metalloproteinase-dependent tumor cell invasion. Surgery, 127(2), 142-147. https://doi.org/10.1067/msy.2000.101155