| Autor: |
Mourskaia, A. A., Dong, Z., Ng, S., Banville, M., Zwaagstra, J. C., O'Connor-McCourt, M. D., Siegel, P. M. |
| Předmět: |
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| Zdroj: |
Oncogene; 2/19/2009, Vol. 28 Issue 7, p1005-1015, 11p, 1 Color Photograph, 5 Graphs |
| Abstrakt: |
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.Oncogene (2009) 28, 1005–1015; doi:10.1038/onc.2008.454; published online 15 December 2008 [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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