Transforming growth factor-β1 is the predominant isoform required for breast cancer cell outgrowth in bone

被引:0
作者
A A Mourskaia
Z Dong
S Ng
M Banville
J C Zwaagstra
M D O'Connor-McCourt
P M Siegel
机构
[1] McGill University,Department of Medicine
[2] McGill University,Department of Anatomy and Cell Biology
[3] Biotechnology Research Institute,Department of Biochemistry
[4] National Research Council of Canada,undefined
[5] McGill University,undefined
来源
Oncogene | 2009年 / 28卷
关键词
TGF-β isoforms; breast cancer; ligand trap; bone microenvironment;
D O I
暂无
中图分类号
学科分类号
摘要
Transforming growth factor (TGF)-β signaling is a potent modulator of the invasive and metastatic behavior of breast cancer cells. Indeed, breast tumor responsiveness to TGF-β is important for the development of osteolytic bone metastases. However, the specific TGF-β isoforms that promote breast cancer outgrowth in bone is unknown. We demonstrate that expression of a TGF-β ligand trap, which neutralizes TGF-β1 and TGF-β3, in MDA-MB-231 breast cancer cells diminished their outgrowth in bone and reduced the severity of osteolytic lesion formation when compared with controls. We further show that a reduction or loss of TGF-β1 expression within the bone microenvironment of TGF-β1+/− and TGF-β1−/− mice significantly reduced the incidence of breast tumor outgrowth compared with wild-type animals. Interestingly, those tumors capable of growing within the tibiae of TGF-β1-deficient mice had upregulated expression of all three TGF-β isoforms. Finally, breast cancer cells expressing the TGF-β ligand trap showed a pronounced reduction in their ability to form osteolytic lesions when injected into the tibiae of TGF-β1+/− mice. Thus, our studies show that both host- and tumor-derived TGF-β expression plays a critical role during the establishment and outgrowth of breast cancer cells in bone.
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页码:1005 / 1015
页数:10
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