Plasminogen activator inhibitor-1 (PAI-1) modifies the formation of aggressive fibromatosis (desmoid tumor).

Published

Journal Article

Aggressive fibromatosis is a mesenchymal neoplasm associated with mutations, resulting in beta-catenin-mediated transcriptional activation. We found that plasminogen activator inhibitor-1 (PAI-1) was upregulated fourfold in aggressive fibromatosis. We investigated the ability of beta-catenin to regulate a PAI-1 reporter, and found that PAI-1 is an indirect target. To determine the role of PAI-1 in vivo, a mouse containing a targeted deletion in Pai-1 was crossed with a mouse that develops aggressive fibromatosis and gastrointestinal tumors (Apc/Apc1638N mouse). Pai-1 deficiency reduced the number of aggressive fibromatosis tumors formed, but not the number of gastrointestinal tumors. Deficiency of Pai-1 reduced tumor cell proliferation and motility rate. Although PAI-1 can alter cell motility by competing for a common binding site on vitronectin, blocking this site did not alter the motility rate. The number of cells moving through matrigel (invasion rate) did not change with Pai-1 deficiency, but because of the low motility rate the invasion index (invasion rate/motility) was increased in Pai-1-deficient cells. This suggests a proteolytic effect for PAI-1 regulating cell invasiveness. Our study found that, although PAI-1 has cellular effects that could inhibit or enhance tumor growth, on balance, it acts as a tumor enhancer in aggressive fibromatosis.

Full Text

Duke Authors

Cited Authors

  • Fen Li, C; Kandel, C; Baliko, F; Nadesan, P; Brünner, N; Alman, BA

Published Date

  • February 24, 2005

Published In

Volume / Issue

  • 24 / 9

Start / End Page

  • 1615 - 1624

PubMed ID

  • 15674349

Pubmed Central ID

  • 15674349

International Standard Serial Number (ISSN)

  • 0950-9232

Digital Object Identifier (DOI)

  • 10.1038/sj.onc.1208193

Language

  • eng

Conference Location

  • England