Histamine-stimulated expression of insulin-like growth factors in human glioma cells

Abstract

Summary Glioma tumour growth is associated with the expression of insulin-like growth factors and 11 (IGFs) and of both type and type 11 IGF receptors. It has also been shown that IGFs can stimulate proliferation of cultured glioma cells. We previously reported that histamine too can stimulate the growth of glioma cells in vitro. In this report, we study whether the histamine-induced growth of G47 glioma cells is mediated by the IGFs. We found that histamine stimulates the expression of both IGF-I and IGF-11 mRNAs, as determined by a semiquantitative in situ hybridization analysis. Furthermore, incubation of G47 cells with histamine also induced cellular immunostaining for IGF-11. It could be shown that IGF-I-stimulated proliferation is inhibited by IGFBP-3, which decreases the availability of IGFs for binding to the IGF receptors, and by P-galactosidase, which may decrease IGF binding to the type 11 IGF receptor, but is not inhibited by the anti-type IGF receptor monoclonal antibody alR3. However, neither IGFBP-3 nor P-galactosidase nor alR3 inhibited the histamine-induced proliferation. These results show that the growth-stimulatory effect of histamine is accompanied by the induction of IGFs. This histamine-induced growth stimulation is not mediated by activation of cell surface IGF receptors, although intracrine activation of type 11 IGF receptors may be involved.

Histamine deficiency delays ischaemic skeletal muscle regeneration via inducing aberrant inflammatory responses and repressing myoblast proliferation

“…This suggested that the histamine pathway may undertake crosstalk with the IGF‐1R/PI3K/AKT signalling pathway. This is consistent with other reports showing that histamine increased the growth of glioma cells by inducing the expression of IGF‐1, and blocking the proliferation‐inducing effect of supplemented IGF‐I did not affect histamine‐stimulated proliferation . We found that the PI3K antagonist blocked the histamine proliferative effect on C2C12 cells, and the histamine H3 receptor antagonist blocked the histamine effect on C2C12 cell proliferation.…”

“…This is consistent with other reports showing that histamine increased the growth of glioma cells by inducing the expression of IGF-1, and blocking the proliferation-inducing effect of supplemented IGF-I did not affect histamine-stimulated proliferation. 23 We found that the PI3K antagonist blocked the histamine proliferative effect on C2C12 cells, and the histamine H3 receptor antagonist blocked the histamine effect on C2C12 cell proliferation. These results suggest that histamine promotes C2C12 cell proliferation by activating PI3K/AKT via the H3 receptor (H3R).…”

“…In the early‐phase of myoblast differentiation in vitro, high levels of histamine receptor expression can be detected, suggesting that histamine may participate in myoblast proliferation . A previous study also reported that histamine could stimulate the expression of IGF‐1 in human glioma cells . These studies suggest that histamine may have an impact on the proliferation and differentiation of myoblasts and muscle regeneration.…”

“…22 A previous study also reported that histamine could stimulate the expression of IGF-1 in human glioma cells. 23 These studies suggest that histamine may have an impact on the proliferation and differentiation of myoblasts and muscle regeneration.…”

Autocrine Production of Insulin-like Growth Factor-I (IGF-I) Affects Paracellular Transport Across Epithelial CellsIn Vitro

“…However, with intracrine signaling, stimulation occurs before the growth factor can be released to the extracellular environment via interaction with intracellular receptors (Re 2002). In recent years, there has been a growing interest in intracrine signaling, particularly with regard to the endothelial growth factor (EGF) (Wiley et al 1998), FGF (Bilak et al 2003;Stachowiak et al 1997), angiotensin II (Baker et al 2004) and IGF (Dubois et al 1993;Lin et al 1997;Van der Ven et al 1997;Baumrucker 2005) families. In our studies, addition of exogenous growth factors or other effectors, such as IGFBP-3, failed to alter the barrier properties of parental cells; likewise, addition of IGFBP-3 in order to bind endogenously secreted IGF-I did not impact the IGF-I-secreting cell line barrier properties.…”