Send to

Choose Destination
Surgery. 2002 Aug;132(2):220-5.

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

Author information

Department of Surgery, The Medical College of Georgia, Augusta 30912, USA.



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.


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.


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).


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.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center