Systemic sclerosis-endothelial cell antiangiogenic pentraxin 3 and matrix metalloprotease 12 control human breast cancer tumor vascularization and development in mice

Francesca Margheri, Simona Serratì, Andrea Lapucci, Chillà Anastasia, Betti Giusti, Marco Pucci, Eugenio Torre, Francesca Bianchini, Lido Calorini, Adriana Albini, Agostina Ventura, Gabriella Fibbi, Mario Del Rosso

Research output: Contribution to journalArticle

Abstract

We have previously shown that endothelial cell matrix metalloprotease 12 (MMP12) and pentraxin 3 (PTX3) overproduction is the main alteration accounting for reduced proneness to angiogenesis in systemic sclerosis (SSc). On this basis, we stably transfected MMP12 and PTX3 in two breast cancer cell lines expressing very low amounts of the target molecules when compared with normal breast epithelial cells, relying on the hypothesis that antiangiogenic molecules released by cancer cells could confer an SSc-like antiangiogenic pattern on target endothelial cells. In Matrigel Boyden chamber invasion and capillary morphogenesis studies, transfected clones reduced endothelial cell invasion and capillary tube formation, which were abolished by tumor cell populations expressing both molecules. The Matrigel sponge assay, performed in vivo in C57/BL6 mice by injecting aliquots of lyophilized culture medium of transfected clones, indicated a similar reduction in angiogenesis. Functional studies have shown that endothelial cells treated with a culture medium of MMP12-expressing clones underwent cleavage of urokinase-type plasminogen activator receptor domain 1 which is indispensable to angiogenesis. We did not observe angiostatin production fromplasminogen under the same experimental conditions. PTX3-overexpressing clones showed a powerful anti-fibroblast growth factor 2 (FGF2) activity in FGF2-dependent capillary morphogenesis. We have injected control and transfected clones into nude nu/nu (CD-1) BR mice to study the differential tumor growth pattern. We observed a reduction of tumor growth in transfected clones, which was basically complete when clones expressing both molecules were simultaneously injected. The extent of tumor necrosis suggested an antiangiogenesis-dependent inhibition of tumor development.

Original languageEnglish
Pages (from-to)1106-1115
Number of pages10
JournalNeoplasia (United States)
Volume11
Issue number10
DOIs
Publication statusPublished - Oct 2009

ASJC Scopus subject areas

  • Cancer Research

Fingerprint Dive into the research topics of 'Systemic sclerosis-endothelial cell antiangiogenic pentraxin 3 and matrix metalloprotease 12 control human breast cancer tumor vascularization and development in mice'. Together they form a unique fingerprint.

  • Cite this

    Margheri, F., Serratì, S., Lapucci, A., Anastasia, C., Giusti, B., Pucci, M., Torre, E., Bianchini, F., Calorini, L., Albini, A., Ventura, A., Fibbi, G., & Del Rosso, M. (2009). Systemic sclerosis-endothelial cell antiangiogenic pentraxin 3 and matrix metalloprotease 12 control human breast cancer tumor vascularization and development in mice. Neoplasia (United States), 11(10), 1106-1115. https://doi.org/10.1593/neo.09934