Nerve growth factor and receptors are significantly affected by histamine stimulus through H1 receptor in pancreatic carcinoma cells

Abstract

Abstract. nerve growth factor (nGF) as an autocrine or paracrine growth factor plays a critical role in the pathogenesis and progression of human pancreatic cancer. nGF is synthesized as a proform (pronGF) that, when cleaved, releases mature ligand (mnGF). pronGF and mnGF bind to high-affinity tyrosine kinase receptor A (TrkA) and lowaffinity receptor p75 to different extents. Histamine is a potent stimulator of NGF in the inflammatory lesion as determined by eliSa. This has generally been attributed to the accumulation of mnGF. To determine the effect of histamine on nerve growth factor/receptor expression in human pancreatic cancer, the present study explored intracellular and extracellular NGF production and p75 and TrkA membrane receptor expression in the PANC-1, KMP-6 and PK-1 cell lines. Histamine enhanced NGF secretion and mRNA expression in PANC-1 and KMP-6 cells, but not in PK-1 cells. proNGF was revealed using Western blotting to be the predominant form of NGF, but was significantly reduced by histamine. p75 receptor binding was increased with histamine treatement, but no significant alteration was observed for TrkA. Proliferating cell nuclear antigen (Pcna), an important indicator of cell proliferation, was significantly reduced by histamine stimulation. H 1 and H 2 receptors were both observed in the pancreatic cancer cells, and the alterations induced by histamine were counteracted by H 1 receptor antagonist pyrilamine; however, the H 2 receptor subtype was excluded from this process. These results suggest that histamine induces distinct nerve growth factor/receptor responsiveness via H 1 receptor-induced signaling, thus affecting pancreatic cancer cell proliferation.

NGF and proNGF Reciprocal Interference in Immunoassays: Open Questions, Criticalities, and Ways Forward

“…For many years, NGF levels have been measured in biological fluids (Vizzard, 2000 ; Wang et al, 2010 ; Konukoglu et al, 2012 ; Liu and Kuo, 2012 ; Tasset et al, 2012 ; Counts et al, 2016 ) by ELISA, and a very large body of literature reports on correlations between altered levels of “ bona fide ” NGF and various pathological conditions (Vizzard, 2000 ; Lombardi et al, 2008 ; Marksteiner et al, 2008 ; Wang et al, 2010 ; Konukoglu et al, 2012 ; Liu and Kuo, 2012 ; Tasset et al, 2012 ; Ke et al, 2014 ; Camara et al, 2015 ), without taking into consideration the concomitant presence of proNGF in the same samples. However, the open question remains, whether ELISA assays, exploiting anti-NGF antibody pairs, really discriminate between the two neurotrophin forms.…”

Evaluation of the Differences in the Expression of Biogenic Amine-Related mRNAs and Proteins in Endometrioid Endometrial Cancer

“…Histamine and its four receptors (H1–H4 encoded by the HRH1 – HRH4 genes) are mainly involved in inflammatory reactions and may affect the proliferation and angiogenesis of neoplastic cells, favoring the initiation and further progression of cancer [ 6 ]. Changes in their activity have been observed in gastric cancer [ 7 ], pancreatic cancer [ 8 ], colorectal cancer [ 9 ], hepatocellular carcinoma [ 10 ], and cholangiocarcinoma [ 11 ]. The deregulation of the dopaminergic system, the activity that depends on the dopamine D1–D5 receptors (DRD1–DRD5), may also play a role in the proliferation, apoptosis, and migration of breast and colon cancers [ 12 ], ovarian cancer [ 13 ], and gastric cancer [ 14 ].…”