Proliferation Paracrine effects

Hormones transfer signals by migrating from their site of synthesis to their site of action. They are usually transported in the blood. In this case, they are said to have an endocrine effect (1 example insulin). By contrast, tissue hormones, the target cells for which are in the immediate vicinity of the glandular cells that produce them, are said to have a paracrine effect (2 example gastrointestinal tract hormones). When signal substances also pass effects back to the cells that synthesize them, they are said to have an autocrine effect (3 example prostaglandins). Autocrine effects are often found in tumor cells (see p. 400), which stimulate their own proliferation in this way. 

The direct effects opioid and opioidlike peptides exhibit on cells of the immune system is both varied and, in some instances, contradictory, depending on which receptor subtype is being studied. Mu and kappa receptors generally affect immunofunction in a suppressive manner, where delta receptors tend to express immunostimulation [82-85]. However, selected delta antagonists have shown to elicit suppressive effects on B-cell proliferation, NK cell activity, and T-helper cell cytokine production [86]. The alteration of leukocyte function via opioid receptors will be discussed highlighting specific cell subtype immunomodulation. Endorphin shows a inhibitory effect on splenocyte proliferation through central and peripheral autocrine/paracrine pathways [87]. 

From the earlier work discussed at the 1978 Cold Spring Harbor Meeting on Cell Proliferation there has developed a broad field concerned with the study of growth factors and hormones and their effects on cell growth and differentiation. This area is considered in more detail in Chapter 2 and is of enormous clinical importance for the treatment of cancer. As well as the work on peptide hormones much work has focused on the use of MCF-7 and ZR 75.1 cell lines which were isolated from human breast tumour tissue (Lippman et al., 1977 Engel et al., 1978). These cells respond to oestrogen treatment, but the system is not as simple as first thought and may involve paracrine responses (Leake, 1988). 

K.B. Pasumarthi, E. Kardami, and P.A. Cattini, High and low molecular weight fibroblast growth factor-2 increase proliferation of neonatal rat cardiac myocytes but have differential effects on binucleation and nuclear morphology. Evidence for both paracrine and intracrine actions of fibroblast growth factor-2, Circ Res 78, 126-136 (1996). 

A number of cytokines also play important roles in regulating other processes that might contribute to immunosuppression. SIL-2R is released by T lymphocytes stimulated to proliferate by IL-2. IL-1 and TNF induce the synthesis and release of proteinases that might contribute to the production of trauma-derived peptides. The effects of sIL-2R and trauma-derived peptides are probably particularly important at or close to the site of production that is they are acting in a paracrine fashion. 

IGF levels. IGF-I mediates the effects of growth hormone, which is mainly secreted by liver but is also produced in several other tissues. IGF-I can act in an autocrine and paracrine maimer to promote normal growth and malignant cellular proliferation. In vitro, low micromolar concentrations of lycopene have slowed cancer cell proliferation by suppressing response to IGF-I. " There has been considerable progress recently in the understanding of the hormonal causes of prostate cancer. Particularly, a number of studies have shown a positive association between IGF-I and the incidence of prostate cancer, whereas the association was reversed after radical prostatectomy and/or treatment with lycopene. ... 

The therapeutic effects mediated by exosomes from human stem cells are numerous. Exosomes from human CD34(-I-) stem cells mediate proangiogenic paracrine activity to help rebuild vasculature (Sahoo et al., 2011). Adult stem-cell-derived exosomes also shuttle selected patterns of mRNA, miRNA, and pre-miRNA associated with several cellular functions involved in the control of transcription, proliferation, and cell immune regulation. 

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