The Role of TGF-β in Bone Metastases
Complications associated with advanced cancer are a major clinical challenge and, if associated with bone metastases, worsen the prognosis and compromise the survival of the patients. Breast and prostate cancer cells exhibit a high propensity to metastasize to bone. The bone microenvironment is uniq...
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MDPI AG
2021
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oai:doaj.org-article:bcea8097de5c448abc431ca453ee68b02021-11-25T16:53:19ZThe Role of TGF-β in Bone Metastases10.3390/biom111116432218-273Xhttps://doaj.org/article/bcea8097de5c448abc431ca453ee68b02021-11-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1643https://doaj.org/toc/2218-273XComplications associated with advanced cancer are a major clinical challenge and, if associated with bone metastases, worsen the prognosis and compromise the survival of the patients. Breast and prostate cancer cells exhibit a high propensity to metastasize to bone. The bone microenvironment is unique, providing fertile soil for cancer cell propagation, while mineralized bone matrices store potent growth factors and cytokines. Biologically active transforming growth factor β (TGF-β), one of the most abundant growth factors, is released following tumor-induced osteoclastic bone resorption. TGF-β promotes tumor cell secretion of factors that accelerate bone loss and fuel tumor cells to colonize. Thus, TGF-β is critical for driving the feed-forward vicious cycle of tumor growth in bone. Further, TGF-β promotes epithelial-mesenchymal transition (EMT), increasing cell invasiveness, angiogenesis, and metastatic progression. Emerging evidence shows TGF-β suppresses immune responses, enabling opportunistic cancer cells to escape immune checkpoints and promote bone metastases. Blocking TGF-β signaling pathways could disrupt the vicious cycle, revert EMT, and enhance immune response. However, TGF-β’s dual role as both tumor suppressor and enhancer presents a significant challenge in developing therapeutics that target TGF-β signaling. This review presents TGF-β’s role in cancer progression and bone metastases, while highlighting current perspectives on the therapeutic potential of targeting TGF-β pathways.Trupti TrivediGabriel M. PagnottiTheresa A. GuiseKhalid S. MohammadMDPI AGarticlebone metastasestransforming growth factor-β (TGF-β)programmed cell death ligand (PD-L1)immune cellsTGF-β therapeutic targetscheck-point inhibitorsMicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1643, p 1643 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
bone metastases transforming growth factor-β (TGF-β) programmed cell death ligand (PD-L1) immune cells TGF-β therapeutic targets check-point inhibitors Microbiology QR1-502 |
| spellingShingle |
bone metastases transforming growth factor-β (TGF-β) programmed cell death ligand (PD-L1) immune cells TGF-β therapeutic targets check-point inhibitors Microbiology QR1-502 Trupti Trivedi Gabriel M. Pagnotti Theresa A. Guise Khalid S. Mohammad The Role of TGF-β in Bone Metastases |
| description |
Complications associated with advanced cancer are a major clinical challenge and, if associated with bone metastases, worsen the prognosis and compromise the survival of the patients. Breast and prostate cancer cells exhibit a high propensity to metastasize to bone. The bone microenvironment is unique, providing fertile soil for cancer cell propagation, while mineralized bone matrices store potent growth factors and cytokines. Biologically active transforming growth factor β (TGF-β), one of the most abundant growth factors, is released following tumor-induced osteoclastic bone resorption. TGF-β promotes tumor cell secretion of factors that accelerate bone loss and fuel tumor cells to colonize. Thus, TGF-β is critical for driving the feed-forward vicious cycle of tumor growth in bone. Further, TGF-β promotes epithelial-mesenchymal transition (EMT), increasing cell invasiveness, angiogenesis, and metastatic progression. Emerging evidence shows TGF-β suppresses immune responses, enabling opportunistic cancer cells to escape immune checkpoints and promote bone metastases. Blocking TGF-β signaling pathways could disrupt the vicious cycle, revert EMT, and enhance immune response. However, TGF-β’s dual role as both tumor suppressor and enhancer presents a significant challenge in developing therapeutics that target TGF-β signaling. This review presents TGF-β’s role in cancer progression and bone metastases, while highlighting current perspectives on the therapeutic potential of targeting TGF-β pathways. |
| format |
article |
| author |
Trupti Trivedi Gabriel M. Pagnotti Theresa A. Guise Khalid S. Mohammad |
| author_facet |
Trupti Trivedi Gabriel M. Pagnotti Theresa A. Guise Khalid S. Mohammad |
| author_sort |
Trupti Trivedi |
| title |
The Role of TGF-β in Bone Metastases |
| title_short |
The Role of TGF-β in Bone Metastases |
| title_full |
The Role of TGF-β in Bone Metastases |
| title_fullStr |
The Role of TGF-β in Bone Metastases |
| title_full_unstemmed |
The Role of TGF-β in Bone Metastases |
| title_sort |
role of tgf-β in bone metastases |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/bcea8097de5c448abc431ca453ee68b0 |
| work_keys_str_mv |
AT truptitrivedi theroleoftgfbinbonemetastases AT gabrielmpagnotti theroleoftgfbinbonemetastases AT theresaaguise theroleoftgfbinbonemetastases AT khalidsmohammad theroleoftgfbinbonemetastases AT truptitrivedi roleoftgfbinbonemetastases AT gabrielmpagnotti roleoftgfbinbonemetastases AT theresaaguise roleoftgfbinbonemetastases AT khalidsmohammad roleoftgfbinbonemetastases |
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