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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/11/1643 |
| _version_ | 1797511095551787008 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:40:34Z |
| format | Article |
| id | doaj.art-bcea8097de5c448abc431ca453ee68b0 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T05:40:34Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-bcea8097de5c448abc431ca453ee68b02023-11-22T22:34:13ZengMDPI AGBiomolecules2218-273X2021-11-011111164310.3390/biom11111643The Role of TGF-β in Bone MetastasesTrupti Trivedi0Gabriel M. Pagnotti1Theresa A. Guise2Khalid S. Mohammad3Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAComplications 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.https://www.mdpi.com/2218-273X/11/11/1643bone metastasestransforming growth factor-β (TGF-β)programmed cell death ligand (PD-L1)immune cellsTGF-β therapeutic targetscheck-point inhibitors |
| spellingShingle | Trupti Trivedi Gabriel M. Pagnotti Theresa A. Guise Khalid S. Mohammad The Role of TGF-β in Bone Metastases Biomolecules bone metastases transforming growth factor-β (TGF-β) programmed cell death ligand (PD-L1) immune cells TGF-β therapeutic targets check-point inhibitors |
| title | 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_short | The Role of TGF-β in Bone Metastases |
| title_sort | role of tgf β in bone metastases |
| topic | bone metastases transforming growth factor-β (TGF-β) programmed cell death ligand (PD-L1) immune cells TGF-β therapeutic targets check-point inhibitors |
| url | https://www.mdpi.com/2218-273X/11/11/1643 |
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