Growth hormone and colorectal carcinoma: localization of receptors

Growth hormone (GH) plays a crucial role in stimulating and controlling the growth, metabolism and differentiation of many mammalian cell types by modulating the synthesis of multiple mRNA species and a paracrine or autocrine mechanism of action has been proposed. These effects are mediated by the binding of GH to its membrane-bound receptor and involve a phosphorylation cascade that results in the modulation of numerous signaling pathways. To address the side/mode of action through which GH exerts its effects, a panel of well characterized monoclonal antibodies, directed against the hormone binding side of the receptor, was applied to immunohistochemically determine growth hormone receptor (GH-receptor) expression in poorly- moderate- to well differentiated col.orectal adenocarcinomas (n = 40) from the rectum, transverse-, ascending-, descending and sigmoid colons. Of five anti-growth hormone receptor monoclonal antibodies used, human GH- receptor specific Mab 263 consistently resulted in strong receptor expression in colorectal carcinoma tumour cells. Heterogeneity of immunoreactivity was found in primary and secondary tumour lesions with a variable range of positive cells. Staining was mainly intracellular, showing either a monotonous or granular pattern, with some nuclei also reactive. The presence of intracellular GH-receptors has been previously documented and is a result of endoplasmic reticulum and Golgi localization. Immunoreactivity in surface columnar cells, independent from pathological tissue, was weak to moderate. Epithelial cells from normal tissue, adjacent to tumour lesions, were of variable intensity. Goblet and mucous cells located at the crypt base immunostained faintly or were negative for the GH-receptors. Crypt base columnar cells strongly expressed the GH-receptor, but oligomucous cells were less reactive. In conclusion, this study indicates that receptor expression may be associated with malignancy of colorectal carcinoma and supports the hypothesis that GH may act locally in colorectal tissue. The demonstration of the presence of receptors for GH will be useful for site-specific studies of the evolution of gastrointestinal tract tumours, providing valuable information concerning cellular growth kinetics and tumour prognosis. It also raises questions regarding the administration of GH to cancer-induced cachexia patients and the possible oncogenic potential of the GH-receptor.