Disease relevance of Paracrine Communication

• Agouti protein and Agouti-related protein (Agrp) are paracrine-signaling molecules that normally regulate pigmentation and body weight, respectively [1].
• Oxytocin synthesis and oxytocin receptor expression by cell lines of human small cell carcinoma of the lung stimulate tumor growth through autocrine/paracrine signaling [2].
• Lysophosphatidic acid, the substrate for lysophosphatidic acid acyltransferase beta (LPAAT-beta), is a well-studied autocrine/paracrine signaling molecule that is secreted by ovarian cancer cells and is found at elevated levels in the blood and ascites fluid of women with ovarian cancer [3].
• If COX-2 does indeed play a role in the early stages of colorectal carcinogenesis in man, these data suggest COX-2-mediated paracrine signaling between the macrophages and epithelial cells within adenomas [4].
• The humoral hypercalcemia factor parathyroid hormone-related protein is a paracrine-signaling molecule that regulates the development of several organ systems, including the skin [5].

High impact information on Paracrine Communication

• Paracrine signaling through the JAK/STAT pathway activates invasive behavior of ovarian epithelial cells in Drosophila [6].
• We show that in the dorsal follicle cells this initial paracrine signaling event triggers an autocrine amplification by two other EGFR ligands, Spitz and Vein [7].
• Vascular endothelial growth factor and its high-affinity receptor tyrosine kinase flk-1 represent a paracrine signaling system crucial for the differentiation of endothelial cells and the development of the vascular system [8].
• This paracrine communication is modulated by glutamate but not GABA transporters, which do not operate during this period of life [9].
• Using a polarized human intestinal epithelial monolayer (T84), we now characterize the basis of the observed conversion of 5'-AMP to adenosine required for this paracrine signaling pathway [10].

Biological context of Paracrine Communication

• These results indicate that autocrine or paracrine signaling through EGFR potentiates the invasive potential of HNSCC via the selective up-regulation and activation of MMP-9 [11].
• The adenosine triphosphate-P2 receptor cell death pathway suggests that autocrine/paracrine signaling may contribute to regulation of viability in certain cancer cells disclosed with this pathway [12].
• Taken together, these observations demonstrate the existence of a functional OT-mediated autocrine/paracrine signaling actively implicated in growth and development of SCCL tumors [2].
• Our data suggest that vIL-6 and vMIP-1A may influence PEL through VEGF autocrine and paracrine signaling that promotes PEL cell growth and extravascular effusion and that vMIP-1A and vMIP-1B can act independently of VEGF as antiapoptotic factors [13].
• The similarity of its N-terminus to that of parathyroid hormone (PTH) enables it to share PTH's paracrine signaling properties, whereas the rest of the molecule possesses other functions, largely relating to an intracrine signaling role in the nucleus/nucleolus in regulating apoptosis and cell proliferation [14].

Anatomical context of Paracrine Communication

• Bv8 potentially modulates growth, survival, and function of cells of the innate and adaptive immune systems, possibly through autocrine or paracrine signaling mechanisms [15].
• In normal sebaceous glands IHH is expressed in differentiated sebocytes and the transcription factor GLI1 is activated in sebocyte progenitors, suggesting a paracrine signaling mechanism [16].
• The mouse agouti protein is a paracrine signaling molecule that induces hair follicle melanocytes to switch from the synthesis of black pigment to yellow pigment [17].
• gamma-Aminobutyric acid (GABA) has been proposed to function as a paracrine signaling molecule in islets of Langerhans [18].
• Hence, Ang-2 deficiency causes dysmorphogenesis of cortical peritubular capillaries, with adjacent cells expressing pericyte-like markers; we speculate the latter effect is caused by disturbed paracrine signaling between endothelial and surrounding mesenchymal precursor cells [19].

Associations of Paracrine Communication with chemical compounds

• Retinoic acid guides eye morphogenetic movements via paracrine signaling but is unnecessary for retinal dorsoventral patterning [20].
• Autocrine and paracrine signaling by amphiregulin may require cellular heparin-like glycosaminoglycans, presumably as matrix or membrane proteoglycans, whereas soluble glycosaminoglycans inhibit signaling, possibly by competing for cytokine binding [21].
• The stimulatory action of glucose in isolated alpha-cells contrasts with the suppressive effect of the sugar in intact islets and highlights the primary importance of islet paracrine signaling in the regulation of glucagon release [22].
• The agouti locus encodes a novel paracrine signaling molecule containing a signal sequence, an N-linked glycosylation site, a central lysine-rich basic domain, and a C-terminal tail containing 10 cysteine (Cys) residues capable of forming five disulfide bonds [23].
• Co-expression of prostaglandin receptors with opposite effects: a model for homeostatic control of autocrine and paracrine signaling [24].

Gene context of Paracrine Communication

• Here, we show that targeting murine Foxf1 and Foxf2, encoding forkhead transcription factors, has pleiotropic effects on intestinal paracrine signaling [25].
• Thus, activation of TGF-beta at the cell surface was responsible for the increased autocrine endogenous and paracrine signaling [26].
• Yet, the paracrine signaling pathways regulating VEGF production and angiogenesis in thyroid cancer have not been fully elucidated [27].
• However, a small proportion of SOX9-positive cells did not appear to express SRY, possibly reflecting the additional involvement of paracrine signaling in activating Sox9 transcription in these cells [28].
• Together with hepatocyte growth factor/scatter factor (HGF/SF), c-Met receptor forms a paracrine signaling system [29].

References