Fibroblasts promote breast cancer cell invasion by upregulating tumor matrix metalloproteinase-9 production

Thomas N. Wang, Daniel Albo, George P. Tuszynski

Research output: Contribution to journalArticle

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Abstract

Background. Thrombospondin-1 (TSP-1) promotes breast cancer cell invasion of collagen by upregulating matrix metalloproteinase-9 (MMP-9) production. Stromal TSP-1 may play a role in regulating tumor cell invasion. We hypothesize that fibroblasts promote breast cancer cell invasion by upregulating the production of MMP-9 through TSP-1. Methods. MDA-MB-231 human breast carcinoma cells were grown alone or in coculture with human fibroblasts. Gelatin zymography and Western immunoblot analysis for MMP-9 were performed on the coculture cell media and the single cell media. Inhibition of fibroblast-mediated breast tumor cell invasion by an anti-TSP-1 or an anti-MMP-9 antibody was evaluated using a modified Boyden chamber. Results. Coculture experiments showed an increased production of MMP-9 when compared with breast cancer single cell culture or fibroblast single cell culture experiments as demonstrated by zymography and Western immunoblot analysis. Fibroblast-stimulated MMP-9 production was comparable with TSP-1 - stimulated MMP-9 production. Anti-TSP-1 antibody and anti-MMP-9 antibody inhibited fibroblast-stimulated tumor cell invasion to 30% and 26% of controls, respectively (P < .05). Conclusions. Fibroblasts may regulate breast cancer cell invasion by promoting tumor MMP-9 production through TSP-1. Inhibition of stromal TSP-1 stimulation of MMP-9 synthesis may prevent matrix degradation necessary for tumor invasion and metastasis.

Original languageEnglish (US)
Pages (from-to)220-225
Number of pages6
JournalSurgery
Volume132
Issue number2
DOIs
StatePublished - Jan 1 2002

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Matrix Metalloproteinase 9
Thrombospondin 1
Fibroblasts
Breast Neoplasms
Neoplasms
Coculture Techniques
Cell Culture Techniques
Western Blotting
Antibodies
Gelatin
Anti-Idiotypic Antibodies
Collagen
Neoplasm Metastasis

ASJC Scopus subject areas

  • Surgery

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Fibroblasts promote breast cancer cell invasion by upregulating tumor matrix metalloproteinase-9 production. / Wang, Thomas N.; Albo, Daniel; Tuszynski, George P.

In: Surgery, Vol. 132, No. 2, 01.01.2002, p. 220-225.

Research output: Contribution to journalArticle

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abstract = "Background. Thrombospondin-1 (TSP-1) promotes breast cancer cell invasion of collagen by upregulating matrix metalloproteinase-9 (MMP-9) production. Stromal TSP-1 may play a role in regulating tumor cell invasion. We hypothesize that fibroblasts promote breast cancer cell invasion by upregulating the production of MMP-9 through TSP-1. Methods. MDA-MB-231 human breast carcinoma cells were grown alone or in coculture with human fibroblasts. Gelatin zymography and Western immunoblot analysis for MMP-9 were performed on the coculture cell media and the single cell media. Inhibition of fibroblast-mediated breast tumor cell invasion by an anti-TSP-1 or an anti-MMP-9 antibody was evaluated using a modified Boyden chamber. Results. Coculture experiments showed an increased production of MMP-9 when compared with breast cancer single cell culture or fibroblast single cell culture experiments as demonstrated by zymography and Western immunoblot analysis. Fibroblast-stimulated MMP-9 production was comparable with TSP-1 - stimulated MMP-9 production. Anti-TSP-1 antibody and anti-MMP-9 antibody inhibited fibroblast-stimulated tumor cell invasion to 30{\%} and 26{\%} of controls, respectively (P < .05). Conclusions. Fibroblasts may regulate breast cancer cell invasion by promoting tumor MMP-9 production through TSP-1. Inhibition of stromal TSP-1 stimulation of MMP-9 synthesis may prevent matrix degradation necessary for tumor invasion and metastasis.",
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N2 - Background. Thrombospondin-1 (TSP-1) promotes breast cancer cell invasion of collagen by upregulating matrix metalloproteinase-9 (MMP-9) production. Stromal TSP-1 may play a role in regulating tumor cell invasion. We hypothesize that fibroblasts promote breast cancer cell invasion by upregulating the production of MMP-9 through TSP-1. Methods. MDA-MB-231 human breast carcinoma cells were grown alone or in coculture with human fibroblasts. Gelatin zymography and Western immunoblot analysis for MMP-9 were performed on the coculture cell media and the single cell media. Inhibition of fibroblast-mediated breast tumor cell invasion by an anti-TSP-1 or an anti-MMP-9 antibody was evaluated using a modified Boyden chamber. Results. Coculture experiments showed an increased production of MMP-9 when compared with breast cancer single cell culture or fibroblast single cell culture experiments as demonstrated by zymography and Western immunoblot analysis. Fibroblast-stimulated MMP-9 production was comparable with TSP-1 - stimulated MMP-9 production. Anti-TSP-1 antibody and anti-MMP-9 antibody inhibited fibroblast-stimulated tumor cell invasion to 30% and 26% of controls, respectively (P < .05). Conclusions. Fibroblasts may regulate breast cancer cell invasion by promoting tumor MMP-9 production through TSP-1. Inhibition of stromal TSP-1 stimulation of MMP-9 synthesis may prevent matrix degradation necessary for tumor invasion and metastasis.

AB - Background. Thrombospondin-1 (TSP-1) promotes breast cancer cell invasion of collagen by upregulating matrix metalloproteinase-9 (MMP-9) production. Stromal TSP-1 may play a role in regulating tumor cell invasion. We hypothesize that fibroblasts promote breast cancer cell invasion by upregulating the production of MMP-9 through TSP-1. Methods. MDA-MB-231 human breast carcinoma cells were grown alone or in coculture with human fibroblasts. Gelatin zymography and Western immunoblot analysis for MMP-9 were performed on the coculture cell media and the single cell media. Inhibition of fibroblast-mediated breast tumor cell invasion by an anti-TSP-1 or an anti-MMP-9 antibody was evaluated using a modified Boyden chamber. Results. Coculture experiments showed an increased production of MMP-9 when compared with breast cancer single cell culture or fibroblast single cell culture experiments as demonstrated by zymography and Western immunoblot analysis. Fibroblast-stimulated MMP-9 production was comparable with TSP-1 - stimulated MMP-9 production. Anti-TSP-1 antibody and anti-MMP-9 antibody inhibited fibroblast-stimulated tumor cell invasion to 30% and 26% of controls, respectively (P < .05). Conclusions. Fibroblasts may regulate breast cancer cell invasion by promoting tumor MMP-9 production through TSP-1. Inhibition of stromal TSP-1 stimulation of MMP-9 synthesis may prevent matrix degradation necessary for tumor invasion and metastasis.

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