TGF-β is a critical driver for macrophages adopting the M2 phenotype [ 168 ], which produce cytokines and chemokines including MMP9, CXCL8, CXCL12, VEGF, and IL-10 that induce tumor growth and invasion, modify the ECM and promote angiogenesis.
Full Answer
What is the role of TGF beta in cancer?
TGFbeta in Cancer The transforming growth factor beta (TGFbeta) signaling pathway is a key player in metazoan biology, and its misregulation can result in tumor development. The regulatory cytokine TGFbeta exerts tumor-suppressive effects that cancer cells must elude for malignant evolution.
Is the TGF-β pathway a promising target for cancer treatment?
Targeting the TGF-β pathway can be a promising direction in cancer treatment. However, several challenges still exist, the most important are differentiating between the carcinogenic effects of TGF-β and its other physiological roles, and delineating the tumor suppressive versus the tumor promoting roles of TGF-β in each specific tumor.
What does TGF-β do to cytotoxic T cells?
Thomas, D. A. & Massagué, J. TGF-β directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. Cancer Cell 8, 369–380 (2005). 99. Castriconi, R. et al. Transforming growth factor β1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells.
What is the role of TGF-beta-ri kinase inhibitors in melanoma?
Mohammad KS, Javelaud D, Fournier PG, Niewolna M, McKenna CR, Peng XH. et al. TGF-beta-RI kinase inhibitor SD-208 reduces the development and progression of melanoma bone metastases. Cancer Res. 2011;71:175–84. [PMC free article][PubMed] [Google Scholar] 113.
What is the role of TGF-beta in cell growth?
What is the function of TGF-beta?
What is TGF beta?
Is TGF a tumor suppressor?
Does TGF- induce EMT?
Do tumor cells respond to TGF-?
Is TGF a pro-angiogenic factor?
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What does TGF-beta do in cancer?
TGF-β plays a crucial role in cancer, acting as a tumor suppressor during the initial stages of tumorigenesis. In normal epithelial cells, TGF-β can inhibit cell proliferation, while it also promotes cell differentiation and apoptosis.
What is TGF-beta used for?
Transforming growth factor β (TGF-β) is a highly pleiotropic cytokine that plays an important role in wound healing, angiogenesis, immunoregulation and cancer. The cells of the immune system produce the TGF-β1 isoform, which exerts powerful anti-inflammatory functions, and is a master regulator of the immune response.
Do cancer cells secrete TGF-beta?
TGF-β can be produced by the tumor cell itself or other cells in the tumor microenvironment including stromal cells, macrophages and platelets [81–83]. Additionally, secreted TGF-β that is stored in the extracellular matrix can be release by the tumor-associated increase in matrix degradation factors [84–86].
What does TGF-beta inhibit?
As an immunosuppressive cytokine, TGF-β inhibits the development, proliferation, and activation of immune cells including T cells (CD4+ effector T cells and CD8+ cytotoxic T cells), NK cells, and macrophages [2,14].
Is TGF-beta a tumor suppressor?
TGF-beta inhibits proliferation and induces apoptosis in various cell types, and accumulation of loss-of-function mutations in the TGF-beta receptor or Smad genes classify the pathway as a tumor suppressor in humans.
What does the tgfb1 gene do?
The TGFβ-1 protein triggers chemical signals that regulate various cell activities inside the cell, including the growth and division (proliferation) of cells, the maturation of cells to carry out specific functions (differentiation), cell movement (motility), and controlled cell death (apoptosis).
What does high TGF beta mean?
What does it mean if your TGF-b1 result is too high? - TGF B-1 is often chronically over-expressed in disease states, including cancer, fibrosis and inflammation. - TGF B-1 is moderately to extremely high in Chronic Inflammatory Response Syndrome due to water-damaged buildings (CIRS).
Is TGF beta an oncogene?
TGF-β is a potent proliferation inhibitor of normal colon epithelial cells and acts as a tumor suppressor. However, TGF-β also promotes invasion and metastasis during late-stage CRC, thereby acting as an oncogene.
What does TGF B bind to?
The TGF beta ligand binds to a type II receptor dimer, which recruits a type I receptor dimer forming a hetero-tetrameric complex with the ligand. These receptors are serine/threonine kinase receptors.
What is the difference between TGF beta 1 and 2?
TGF-beta 1 is involved in hematopoiesis and endothelial differentiation; TGF-beta 2 affects development of cardiac, lung, craniofacial, limb, eye, ear, and urogenital systems.
What is TGF in immunology?
Transforming growth factor (TGF)-b is a crucial enforcer of immune homeostasis and tolerance, inhibiting the expansion and function of many components of the immune system.
What does low TGF-beta mean?
2006), the lack of TGF-β could promote local and systemic cell proliferation, which is increased in patients with severe and chronic skin pathology (Timmann et al. 2003). TGF-β not only suppresses immune cells, but can also promote fibrous tissue generation and fibrosis.
What is the role of TGFbeta in metazoan biology?
The transforming growth factor beta (TGFbeta) signaling pathway is a key player in metazoan biology, and its misregulation can result in tumor development. The regulatory cytokine TGFbeta exerts tumor-suppressive effects that cancer cells must elude for malignant evolution. Yet, paradoxically, TGFbeta also modulates processes such as cell invasion, ...
Is TGFbeta a tumor suppressor?
The regulatory cytokine TGFbeta exerts tumor-suppressive effects that cancer cells must elude for malignant evolution. Yet, paradoxically, TGFbe ….
Does TGFbeta affect cancer?
Yet, paradoxically, TGFbeta also modulates processes such as cell invasion, immune regulation, and microenvironment modification that cancer cells may exploit to their advantage. Consequently, the output of a TGFbeta response is highly contextual throughout development, across different tissues, and also in cancer.
What is the TME in cancer?
The TME consists of ECM, cytokines, and a large population of different cell types, including resident and infiltrating CAFs, immune-related cells, endothelial cells, and adipocytes that surround the tumor cells . The multipronged effects of TGFβ on tumor stroma cells built the TME, including its capacity to stimulate ECM production, activate CAFs, suppress the immune system, and promote angiogenesis. Notably, tumor stromal cells are also the main sources of inflammatory factors, including TGFβ. Reciprocally, the TME exerts profound effects on tumor growth and progression. In this section, we summarize the functions of TGFβ in the TME (Fig. 5 ).
What are CAFs in TME?
CAFs are key components of the TME and play roles in providing a favorable environment to support tumor progression by producing ECM and cytokines, stimulating immune evasion, and promoting angiogenesis. 132, 133, 134 Next to tumor-promoting CAFs, also tumor-suppressive CAFs have been identified. 135 Within a tumor, the CAF population can be highly heterogeneous. For example in breast tumors, at least four distinct CAF subpopulations, that is, vascular CAFs, matrix CAFs, cycling CAFs, and developmental CAFs (dCAFs), were defined. 136 In pancreatic tumors, CAFs have been classified into inflammatory CAFs, which are found distant from tumor foci with high IL6 and low α-smooth muscle actin (α-SMA) expression, and myofibroblastic CAFs that are located adjacent to tumor foci with high α-SMA expression and that demonstrate a strong TGFβ responsiveness. 137, 138, 139 The characterization of molecular markers and mechanistic insights of different CAF subtypes may provide opportunities for their precise targeting in cancer therapy. 140
How does chemotherapy work?
Chemotherapy is a frequent standard first-line cancer therapy regimen consisting of one or more anticancer chemicals designed to stop and kill rapidly proliferating cancer cells. However, chemotherapy has strong side effects due to its toxicity to normal cells. Targeted therapy is performed by using small molecules that interfere with specific signaling pathways that promote cancer cell proliferation and survival. 256 Examples of such small-molecule compounds are selective tyrosine kinase inhibitors. 257 Selective small-molecule inhibitors have less severe side effects than standard chemotherapy, but both types of therapy can lead to therapy resistance and relapse, as some cells within the heterogeneous tumor population survive and proliferate after an initial beneficial anticancer response. 258 TGFβ-induced cancer cell acquisition of a mesenchymal phenotype has emerged as a key mechanism that confers the therapy-resistant and stemness phenotype to cancer cells. 22 Blocking TGFβ may kill two birds with one stone by impairing metastasis and preventing resistance against anticancer treatments.
Can mesenchymal cancer cells be metastasized?
Mesenchymal cancer cells have been linked to metastasis and chemotherapy, targeted therapy, and/or radiotherapy resistance. As most cancer patients die of metastasis and demonstrate relapse after chemotherapy, targeted therapy, and/or radiotherapy, the combination of these therapies with TGFβ inhibitors are being tested.
What is the role of TGF-beta in cell growth?
The transforming growth factor-beta (TGF-β ) belongs to a superfamily of cytokines that act on protein kinase receptors at the plasma membrane to induce a plethora of biological signals that regulate cell growth and death, differentiation, immune response, angiogenesis and inflammation. Dysregulation of its pathway contributes to a broad variety ...
What is the function of TGF-beta?
The transforming growth factor-beta (TGF-β ) belongs to a superfamily of cytokines that act on protein kinase receptors at the plasma membrane to induce a plethora of biological signals that regulate cell growth and death, differentiation, immune response, angiogenesis and inflammation. Dysregulatio ….
What is TGF beta?
TGF-beta signaling in cancer treatment. The transforming growth factor-beta ( TGF-β ) belongs to a superfamily of cytokines that act on protein kinase receptors at the plasma membrane to induce a plethora of biological signals that regulate cell growth and death, differentiation, immune response, angiogenesis and inflammation. Dysregulatio …. ...
Is TGF a tumor suppressor?
Dysregulation of its pathway contributes to a broad variety of pathologies, including cancer. TGF-β is an important regulatory tumor suppressor factor in epithelial cells, where it early inhibits proliferation and induces apoptosis. However, tumor cells develop mechanisms to overcome the TGF-β -induced suppressor effects.
Does TGF- induce EMT?
Indeed, TGF-β induces epithelial-mesenchymal transition (EMT), a process that is favored in tumor cells and facilitates migration and invasion. Furthermore, TGF-β mediates production of mitogenic growth factors, which stimulate tumor proliferation and survival.
Do tumor cells respond to TGF-?
However, tumor cells develop mechanisms to overcome the TGF-β -induced suppressor effects. Once this occurs, cells may respond to this cytok ine inducing other effects that contribute to tumor progression.
Is TGF a pro-angiogenic factor?
Finally, TGF-β is a well known immunosuppressor and pro-angiogenic factor. Many studies have identified the overexpression of TGF-β 1 in various types of human cancer, which correlates with tumor progression, metastasis, angiogenesis and poor prognostic outcome.