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01-07-2009 | Preclinical Study

Matrix metalloproteinase-1 promotes breast cancer angiogenesis and osteolysis in a novel in vivo model

Authors: S. M. Eck, P. J. Hoopes, B. L. Petrella, C. I. Coon, C. E. Brinckerhoff

Published in: Breast Cancer Research and Treatment | Issue 1/2009

Abstract

Matrix metalloproteinase-1 (MMP-1) is critical for mediating breast cancer metastasis to bone. We investigated the role of MMP-1 in breast cancer invasion of soft tissues and bone using human MDA MB-231 breast cancer cells stably transfected with shRNAs against MMP-1 and a novel murine model of bone invasion. MMP-1 produced by breast cancer cells with control shRNA facilitated invasion of tumors into soft tissue in vivo, which correlated with enhanced blood vessel formation at the invasive edge, compared to tumors with silenced MMP-1 expression. Tumors expressing MMP-1 were also associated with osteolysis in vivo, whereas tumors with inhibited MMP-1 levels were not. Additionally, tumor-secreted MMP-1 activated bone-resorbing osteoclasts in vitro. Together, these data suggest a mechanism for MMP-1 in the activation of osteoclasts in vivo. We conclude that breast cancer-derived MMP-1 mediates invasion through soft tissues and bone via mechanisms involving matrix degradation, angiogenesis, and osteoclast activation.

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Title: Matrix metalloproteinase-1 promotes breast cancer angiogenesis and osteolysis in a novel in vivo model
Authors: S. M. Eck
P. J. Hoopes
B. L. Petrella
C. I. Coon
C. E. Brinckerhoff
Publication date: 01-07-2009
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 1/2009
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-008-0085-3

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