Paracrine growth factors

PDGF plays an important role in the wound healing process. It is released at the site of damage by activated platelets, and acts as a mitogen/chemoattractant for many of the cells responsible for initiation of tissue repair. It thus tends to act primarily in a paracrine manner. It also represents an autocrine/paracrine growth factor for a variety of malignant cells. 

Recent studies showed that rituximab down-regulates interleukin-10 (lL-10) in some lymphoma cell lines (17,18,19,20,21,22,23,24,25,26,27). IL-10 has a stimulatory function as an autocrine or paracrine growth factor for lymphoma cells (28). lL-10 is a known promoter of BCL2 expression in hematopoietic cells (29) as well as lymphoma cells (28). Rituximab is known to induce down-regulation of lL-10 expression and consequently of bcl-2 protein expression, making B-cells more susceptible to apoptotic signals (Fig. 1) (30,31,32). However, the implication of lL-10 on clinical outcome after rituximab therapy is still unclear. 

Froberg K, Brown RE, Gaylord H, Manivel G. Intra-abdominal desmoplastic small round cell tumor immunohistochemical evidence for up-regulation of autocrine and paracrine growth factors. Ann Clin Lab Sci. 1998 28 386-393. 

GH is only one of many honnones involved in growth. Others are thyroxine, cortisol, the sex steroids, insulin, and a number of paracrine growth factors, particularly the somatomedins or insulin-like growth factors (IGFs) which mediate the growth promoting effects ol growth hormone. 

Kras, K.M., Hausman, D.B., and Martin, R.J. 2000. Tumor necrosis factor-alpha stimulates cell proliferation in adipose tissue-derived stromal-vascular cell culture Promotion of adipose tissue expansion by paracrine growth factors. Obes. Res. 8, 186-193. 

IGF-l is considered to be the main anabolic factor for chondrocyte growth, proliferation, and survival (Van der Kraan et al., 2002, Davies et al., 2008, Starkman et al., 2005). It is structurally similar to insulin and consists of a single chain of 70 amino acids, with a molecular weight of 7.5 kDa (Baserga et al., 1997). IGF functions as an endocrine, autocrine, and paracrine growth factor (Starkman et al., 2005,... 

Table 10.1 Overview of some polypeptide growth factors. Many can be grouped into families on the basis of amino acid sequence homology, or the cell types affected. Most growth factors are produced by more than one cell type and display endocrine, paracrine or autocrine effects on target cells by interacting with specific cell surface receptors...

The factors are secreted into the extracellular milieu where they diffuse and then act in a paracrine fashion on other cells (Fig. 27-1). Indeed, there is evidence that this type of paracrine support is necessary to sustain neurons as they extend their processes over long distances in the developing nervous system [2]. An analogous process, autocrine stimulation, occurs when a cell synthesizes and secretes a growth factor to which the cell itself is responsive. In this case, the cell provides its own trophic support. 

The receptor for NGF is TrkA, a 140 kDa cell surface protein that specifically binds NGF, but not other neurotrophins [5, 6, 9]. TrkA is expressed on the neuronal cell body and on neuronal processes. In its action as a target-derived trophic factor, NGF is secreted within the target organ and it then binds to TrkA receptors present on the growing neuronal process or synapse. The NGF-TrkA complex is then internalized and subsequently translocated to the cell body by retrograde axonal transport. In those cells that respond to NGF through autocrine or paracrine mechanisms, the growth factor can bind to any of the widely distributed TrkA molecules on the neuronal membrane. 

The humoral factors include numerous cytokines and growth factors, which act as classical endocrine, paracrine or autocrine regulators. Developing cells are sensitive to a range of such factors at all times during their maturation and, in the case of white blood cells, during their existence within the circulation. To ensure responsiveness during their development, cells must express on their surface a variety of receptors at different times. 

Fibroblast growth factor-10 (FGF-10) Autocrine/paracrine Preadipocytes Promotes adipogenesis... 

Morganti-Kossmann MC, Kossmann T, Brandes ME, Mergenhagen SE, Wahl SM Autocrine and paracrine regulation of astrocyte function by transforming growth factor-(5. J Neuroimmunol 1992 39 163-173. 

Kitamura M, Suto T, Yokoo T, Shimizu F, Fine LG Transforming growth factor-(Jj is the predominant paracrine inhibitor of macrophage cytokine synthesis produced by glomerular mesangial cells. J Immunol 1996 156 2964-2971. 

S. Goswami, E. Sahai, J. B. Wyckoff, M. Cammer, D. Cox, F. J. Pixley, E. R. Stanley, J. E. Segall, and J. S. Condeelis, Macrophages promote the invasion of breast carcinoma cells via a colony-stimulating factor-1/epidermal growth factor paracrine loop. Cancer Res. 65(12), 5278-5283 (2005). 

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