HISTAMINE-STIMULATED EXPRESSION OF INSULIN-LIKE GROWTH-FACTORS IN HUMAN GLIOMA-CELLS

Glioma tumour growth is associated with the expression of insulin-like growth factors I and II (IGFs) and of both type I and type II IGF rec eptors. It has also been shown that IGFs can stimulate proliferation o f cultured glioma cells. We previously reported that histamine too can stimulate the growth of glioma cells in vitro. In this report, we stu dy whether the histamine-induced growth of G47 glioma cells is mediate d by the IGFs. We found that histamine stimulates the expression of bo th IGF-I and IGF-II mRNAs, as determined by a semiquantitative in situ hybridization analysis. Furthermore, incubation of G47 cells with his tamine also induced cellular immunostaining for IGF-II. It could be sh own that IGF-I-stimulated proliferation is inhibited by IGFBP-3, which decreases the availability of IGFs for binding to the IGF receptors, and by beta-galactosidase, which may decrease IGF binding to the type II IGF receptor, but is not inhibited by the anti-type I IGF receptor monoclonal antibody alpha IR3. However, neither IGFBP-3 nor beta-galac tosidase nor alpha IR3 inhibited the histamine-induced proliferation. These results show that : the growth-stimulatory effect of histamine i s accompanied by the induction of IGFs. This histamine-induced growth stimulation is not mediated by activation of cell surface IGF receptor s, although intracrine activation of type II IGF receptors may be invo lved.