Invasion and MMP expression profile in desmoid tumours.

Published

Journal Article

Desmoid tumours are locally invasive soft tissue tumours in which beta-catenin mediated TCF-dependent transcription is activated. The role of soluble factors secreted by the myofibroblastic desmoid tumour, which could stimulate tumour invasiveness, was investigated. Using collagen gel invasion assays, the presence of factors stimulating invasion in desmoid conditioned media (CM) could be established. Since matrix metalloproteinases (MMPs) have been implicated in the process of tumoral invasion, the expression levels of the MMP family members were evaluated. Quantitative reverse transcription-PCR was used to determine the expression levels of MMP1, MMP2, MMP3, MMP7, MMP11, MMP12, MMP13, MMP14 and the inhibitors TIMP1, TIMP2 and TIMP3. Besides overexpression of MMP7, a known TCF-dependent target gene, a striking upregulation of the expression levels of MMP1, MMP3, MMP11, MMP12 and MMP13 in desmoid tumours, compared to unaffected fibroblasts from the same patients, was found. Treating the CM of desmoids with a synthetic and a physiologic MMP inhibitor reduced the invasion-stimulating capacity of the desmoid CM by approximately 50%. These results suggest the involvement of soluble factors, released by the desmoid cells, in stimulating invasion and implicate the MMPs as facilitators of invasion.

Full Text

Duke Authors

Cited Authors

  • Denys, H; De Wever, O; Nusgens, B; Kong, Y; Sciot, R; Le, A-T; Van Dam, K; Jadidizadeh, A; Tejpar, S; Mareel, M; Alman, B; Cassiman, J-J

Published Date

  • April 5, 2004

Published In

Volume / Issue

  • 90 / 7

Start / End Page

  • 1443 - 1449

PubMed ID

  • 15054469

Pubmed Central ID

  • 15054469

International Standard Serial Number (ISSN)

  • 0007-0920

Digital Object Identifier (DOI)

  • 10.1038/sj.bjc.6601661

Language

  • eng

Conference Location

  • England