Growth Hormone in Vascular Pathology: Neovascularization and Expression of Receptors is Associated with Cellular Proliferation

• Published in: Anticancer research 2007-11, Vol.27 (6B), p.4201-4218
• Main Authors: LINCOLN, D. T, SINGAL, P. K, AL-BANAW, A
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Binding Sites; Biological and medical sciences; Cell Growth Processes - physiology; Female; Growth Hormone - metabolism; Hemangioma - blood supply; Hemangioma - metabolism; Hemangioma - pathology; Humans; Male; Medical sciences; Mice; Mice, Inbred BALB C; Middle Aged; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Rabbits; Rats; Receptors, Somatotropin - biosynthesis; Receptors, Somatotropin - immunology; Receptors, Somatotropin - metabolism; Tumors; Vascular Neoplasms - blood supply; Vascular Neoplasms - metabolism; Vascular Neoplasms - pathology
• ISSN: 0250-7005; 1791-7530

Vascular tumours are common lesions of the skin and subcutaneous tissue, but also occur in many other tissues and internal organs. The well-differentiated tumours consist of irregular anastomosing, blood-filled vascular channels that are lined by variably atypical endothelial cells. The less differentiated tumours may show solid strands and sheets, resembling carcinoma or lymphoma. Several growth factors, including basic fibroblast growth factor, transforming growth factors and vascular endothelial growth factor, play a role in tumour angiogenesis. Growth hormone (GH) is mitogenic for a variety of vascular tissue cells, including smooth muscle cells, fibroblasts and endothelial cells and exerts its regulatory functions in controlling metabolism, balanced growth and differentiated cell expression by acting on specific membrane-bound receptors, which trigger a phosphorylation cascade resulting in the modulation of numerous signalling pathways and of gene expression. Essential to 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. To address the site/mode of action through which GH exerts its effects, a well characterized monoclonal antibody, obtained by hybridoma technology from Balb/c mice immunized with purified rabbit and rat liver GH-receptor (GHR) and directed against the hormone binding site of the receptor, was applied, using the ABC technique to determine GHR expression in a panel of vascular tumours. The GHR was cloned from a rabbit liver cDNA library with the aid of an oligonucleotide probe based on a 19 residue tryptic peptide sequence derived from 5900 fold purified rabbit liver receptor. A total of 64 benign and malignant vascular tumours were obtained from different human organ sites, including the chest wall, skin, axillary contents, duodenum, female breast, abdomen, stomach, colon, lymph node, bladder, body flank and neck regions. The tumours were of the following pathological entities: Haemangioma (n=12); haemangioendothelioma (n=10); Castleman's disease (n=3), haemangiopericytoma (n=4); angiosarcoma, (n=11), Kaposi's sarcoma with focal infiltration by lymphoma, HIV +ve (n=7), Kaposi's sarcoma (n=17). The endothelial cell marker CD-31 was used to establish endothelial cell characteristics and microvascular density. To delineate tumour cell growth, immunohistochemical analysis of cycling nuclear protein and of proliferating cell nuclear