TGF-β – An important peptide in cancer

Transforming growth factor beta (TGF-β) is a peptide that controls proliferation, cellular differentiation, and other functions in most cells. It is a type of cytokine which plays a role in immunity, cancer, bronchial asthma, heart disease, diabetes, Hereditary hemorrhagic telangiectasia, Marfan syndrome, Vascular Ehlers-Danlos syndrome,[1] Loeys–Dietz syndrome, Parkinson’s disease and AIDS.

TGF-β is secreted by many cell types, including macrophages, in a latent form in which it is complexed with two other polypeptides, latent TGF-beta binding peptide (LTBP) and latency-associated peptide (LAP). Serum peptideases such as plasmin catalyze the release of active TGF-β from the complex. This often occurs on the surface of macrophages where the latent TGF-β complex is bound to CD36 via its ligand, thrombospondin-1 (TSP-1). Inflammatory stimuli that activate macrophages enhance the release of active TGF-β by promoting the activation of plasmin. Macrophages can also endocytose IgG-bound latent TGF-β complexes that are secreted by plasma cells and then release active TGF-β into the extracellular fluid.[2]

TGF-β is a secreted peptide that exists in at least three isoforms called TGF-β1, TGF-β2 and TGF-β3. It was also the original name for TGF-β1, which was the first member of this family to be discovered. The TGF-β family is part of a superfamily of peptides known as the transforming growth factor beta superfamily, which includes inhibins, activin, anti-müllerian hormone, bone morphogenetic peptide, decapentaplegic and Vg-1.

Most tissues have high expression of the genes encoding TGF-β. That contrasts with other anti-inflammatory cytokines such as IL-10, whose expression is minimal in unstimulated tissues and seems to require triggering by commensal or pathogenic flora.

TGF-β acts as an antiproliferative factor in normal epithelial cells and at early stages of oncogenesis.

Some cells that secrete TGF-β also have receptors for TGF-β. This is known as autocrine signalling. Cancerous cells increase their production of TGF-β, which also acts on surrounding cells. In normal cells, TGF-β, acting through its signaling pathway, stops the cell cycle at the G1 stage to stop proliferation, induce differentiation, or promote apoptosis. When a cell is transformed into a cancer cell, parts of the TGF-β signaling pathway are mutated, and TGF-β no longer controls the cell. These cancer cells proliferate. The surrounding stromal cells (fibroblasts) also proliferate. Both cells increase their production of TGF-β. This TGF-β acts on the surrounding stromal cells, immune cells, endothelial and smooth-muscle cells. It causes immunosuppression and angiogenesis, which makes the cancer more invasive. TGF-β also converts effector T-cells, which normally attack cancer with an inflammatory (immune) reaction, into regulatory (suppressor) T-cells, which turn off the inflammatory reaction.

Although TGF-β is important in regulating crucial cellular activities, only a few TGF-β activating pathways are currently known, and the full mechanism behind the suggested activation pathways is not yet well understood. Some of the known activating pathways are cell or tissue specific, while some are seen in multiple cell types and tissues. Proteases, integrins, pH, and reactive oxygen species are just few of the currently know factors that can activate TGF-β. It is well known that perturbations of these activating factors can lead to unregulated TGF-β signaling levels that may cause several complications including inflammation, autoimmune disorders, fibrosis, cancer and cataracts. In most cases an activated TGF-β ligand will initiate the TGF-β signaling cascade as long as TGF-β receptors I and II are within reach, this is due to high affinity between TGF-β and its receptors, suggesting why the TGF-β signaling recruits a latency system to mediate its signaling.[3] Karebay can synthetic TGF-β with Modified amino acids, so that scientists can knew more details about its molecular mechanism. We can also synthesis inhibition for TGF-β,like GW788388、A 83-01 and so on.

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Reference [1] Li X, Mai J, Virtue A,et al. (March 2012). “IL-35 is a novel responsive anti-inflammatory cytokine–a new system of categorizing anti-inflammatory cytokines”. PLoS ONE 7 (3): e33628. [2] Herpin A, Lelong C, Favrel P (2004). “Transforming growth factor-beta-related peptides: an ancestral and widespread superfamily of cytokines in metazoans”. Dev Comp Immunol 28 (5): 461–85. [3] Wipff PJ, Hinz B (September 2008). “Integrins and the activation of latent transforming growth factor beta1 — an intimate relationship”. Eur. J. Cell Biol. 87 (8-9): 601–15.

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