Growth factors

Definition

Growth factors are a heterogeneous group of proteins which through specific binding of transmembrane receptors facilitate interactions between mesenchymal and epithelial cells and regulate many aspects of cellular function, such as survival, proliferation, migration and differentiation. Growth factors are essential for tissue development in the fetal period and for the maintenance of homeostasis in the adult body. The lack of growth factors increases apoptosis. Biologically active growth factors are produced by many types of cells residing in tissues, including mesenchymal stem cells. Depending on type and localization, they play a role in many biological processes, including determination of cell fate, mucosal morphogenesis and regeneration, epithelial turnover, establishing proper neuronal connectivity, or, in a pathological state, tumorigenesis. Growth factors and their receptors can be grouped into families based upon shared structural features, many of which are evolutionarily conserved; homologs of the fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor beta (TGF-beta) families can be found in a vast range of species, from nematodes or Drosophila to higher vertebrates.

Examples of growth factors

• FGF - Fibroblast growth factors (FGF) are a large family of polypeptides acting as local or systemic cell signaling  molecules crucial for embryonic development, as well as tissue repair in the adult organism. Their structure and amino-acid sequence is highly conserved among vertebrates, and they are expressed in many, if not all tissues. They stimulate proliferation and inhibit apoptosis of cells derived from the mesoderm and neuroectoderm. These proteins play an important role in organogenesis, wound healing and angiogenesis. Apart from their function in cell proliferation, migration and differentiation, a subset of FGFs plays an important role in neuronal signal transduction. A characteristic property of FGFs is their high affinity for heparin; they require heparan sulfate to bind to one of the four types of their cell surface receptors. FGFs often signal across epithelial-mesenchymal boundaries stimulating cell proliferation and differentiation. Abnormal expression of FGFs is a factor in cancer pathogenesis .
• EGF - Epidermal growth factor (EGF) is a signalling protein found in multiple body fluids, e.g. milk, saliva, urine, blood plasma or amniotic fluid. EGF binds to the EGFR receptors, which in turn dimerize and induce tyrosine kinase activity. This initiates signalling cascades that affect various biological processes such as ion transportation, cell proliferation and differentiation, apoptosis, embryonic development, organ development or tissue regeneration. Increased EGF/EGFR activity correlates with tumour growth and metastasis, particularly in glioblastomas, and lung, breast, colorectal, ovarian, prostate or pancreatic cancers .
• TGF- β - Transforming growth factor-β (TGFβ) is a signalling protein that plays a role in cell proliferation, differentiation, morphogenesis, tissue homeostasis and regeneration via a serine/threonine kinase complex. There are three known isoforms of TGFβ (TGFβ1, TGFβ2 and TGFβ3), and three types of TGFβ membrane receptors (TGF-β RI, TGF-β RII, TGF-β RIII). The transcriptional response to TGFβ in the cell is determined by the composition of the TGFβ signal transduction system (its ligands, receptors and regulators), its interaction with SMAD proteins, and the epigenetic modifications of target DNA. Most members of the TGFβ family act as paracrine factors on cells near the source .