Membrane type 1 matrix metalloprotease cleaves laminin-10 and promotes cancer cell migration

Elisabeth L. Bair, Ling Chen Man, Kathy McDaniel, Kiyotoshi Sekiguchi, Anne E Cress, Raymond B Nagle, George Timothy Bowden

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Disruption of the extracellular matrix by proteases is crucial for tumor invasion. Laminin-10 (Ln-10) has previously been identified as a substrate for cell migration and cell adhesion, and is present in the basal lamina (BL) of both normal prostate and prostate cancer. Here, we investigate a role for membrane type 1 matrix metalloprotease (MT1-MMP) in modifying this Ln-10-rich BL. MT1-MMP is a transmembrane member of the MMP family that has been demonstrated to be upregulated as prostate cancer progresses from normal to prostate intraepithelial neoplasia to invasive cancer, suggesting a role for MT1-MMP in the invasion of prostate cancer. We show that MT1-MMP cleaves the α5 chain of purified human Ln-10 from its 350-kDa form into 310-, 190-, 160-, and 45-kDa fragments. This cleavage causes a decrease in DU-145 prostate cancer cell adhesion to purified Ln-10, and an increase in transmigration of DU-145 cells through cleaved Ln-10. We also show that prostate cancer cells expressing membrane-bound MT1-MMP cleave the α5 chain of Ln-10. Ln α5-chair: cleavage is also observed in human prostate cancer tissues. These findings suggest that prostate cancer cells expressing high levels of MTI-MMP have increased invasive potential through their ability to degrade and invade Ln-10 barriers.

Original languageEnglish (US)
Pages (from-to)380-389
Number of pages10
JournalNeoplasia
Volume7
Issue number4
DOIs
Publication statusPublished - Apr 2005

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Keywords

  • Invasion
  • Laminin-10
  • MMP-14
  • MT1-MMP
  • Prostate

ASJC Scopus subject areas

  • Cancer Research

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