Human colorectal carcinoma is a direct target tissue for growth hormone: Evidence of receptor adaptation

Lincoln, DT, Temmim, L, Al-Jarallah, MA, Abul, HT, Clarke, F and Waters, MJ (2002). Human colorectal carcinoma is a direct target tissue for growth hormone: Evidence of receptor adaptation. In: Moravec, J, Takeda, N and Singal, PK, Adaptation Biology and Medicine, Vol 3: New Frontiers. 6th World Congress of the International-Society-for-Adaptive-Medicine, Lyon France, (267-288). Aug 30-Sep 02, 2000.

Author Lincoln, DT
Temmim, L
Al-Jarallah, MA
Abul, HT
Clarke, F
Waters, MJ
Title of paper Human colorectal carcinoma is a direct target tissue for growth hormone: Evidence of receptor adaptation
Conference name 6th World Congress of the International-Society-for-Adaptive-Medicine
Conference location Lyon France
Conference dates Aug 30-Sep 02, 2000
Proceedings title Adaptation Biology and Medicine, Vol 3: New Frontiers
Journal name Adaptation Biology and Medicine, Vol 3: New Frontiers
Place of Publication NEW DELHI
Publisher NAROSA PUBLISHING HOUSE
Publication Year 2002
Year available 2002
Sub-type Fully published paper
Open Access Status Not yet assessed
ISBN 81-7319-422-X
Editor Moravec, J
Takeda, N
Singal, PK
Start page 267
End page 288
Total pages 22
Language eng
Abstract/Summary Growth hormone (GH) has several distinct roles in intestinal physiology, including hypertrophy of the gastrointestinal tract tissue to supra-normal levels, an induction of mitotic activity in the duodenal epithelium and the crypts of Lieberkuhn and control of normal intestinal growth and differentiation during late foetal and early neonatal. life. Growth hormone is also a potent anabolic agent and has great potential as an adjunct to nutritional support of cachectic patients. These effects are mediated by the binding of GH to its membrane-bound receptor and involve a phosphorylation cascade that result in the modulation of numerous signaling pathways and a paracrine or autocrine mechanism of action has been proposed. Essential for the initiation of a cellular response to GH, the presence of receptors for this hormone may predict the adaptation of tumour cells resulting from GH exposure. Changes in the level of hormones/growth factors or their receptors may be important in the pathogenesis of tumours of the intestinal tract. To address the side/mode of action through which GH exerts its effects, a panel of well characterized monoclonal antibodies, directed against the extracellular hormone binding side of the receptor, was applied to determine GH-receptor expression in poorly-, moderate- and well differentiated colorectal adenocarcinomas (n = 40) from the rectum, transverse-, ascending-, descending and sigmoid colons. In this investigation we report the adaptation of GH-receptors in human colorectal carcinomas. The results provide evidence that GH acts directly on colorectal adenocarcinoma cells to modify their proliferative rate or function. 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 tumour lesions with a variable range of positive cells. The presence of intracellular GH-receptors is a result of endoplasmic reticulum and Golgi localization. Receptor expression in surface columnar cells, independent from pathological tissue, was weak to moderate. Epithelial cells from normal colon tissue, adjacent to tumour lesions, were of variable immunoreactivity. Goblet and mucous cells located at the crypt base immunostained faintly or were negative for the GH-receptors. Proliferative crypt base columnar cells strongly expressed the GH-receptor, but oligomucous cells were less reactive. Tumours in which the great majority of more than 70% cells expressed GH-receptor immunoreactivity were generally of advanced Duke's C stage. These tumours had secondary metastatic lymph node deposits and the majority were located in the distal sigmoid/rectum. In contrast, fewer tumour cells were immunopositive in less advanced colon cancers of Duke's B stage. In conclusion, this study indicates that receptor expression may be associated with malignancy of colorectal carcinoma and supports the hypothesis that GH can act locally in colorectal tissue. The demonstration of the presence of GH-receptors implies that receptor adaptation is a function of colorectal carcinoma progression and malignancy and 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.
Keyword Gh-Binding-Protein
Factor-I
Colon Cancer
Immunohistochemical Localization
Monoclonal-Antibodies
Gene-Expression
Rabbit Liver
C-Myc
Insulin
Serum
Q-Index Code E1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Conference Paper
Sub-type: Fully published paper
Collection: ResearcherID Downloads - Archived
 
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