Up-regulation of growth hormone receptor immunoreactivity in human melanoma.
Growth hormone (GH) exerts its regulatory functions in controlling metabolism, balanced growth and differentiated cell expression by acting on specific receptors, which trigger a phosphorylation cascade resulting in the modulation of numerous signalling pathways, and dictate gene expression. Immunohistochemical techniques were used to demonstrate the presence of growth hormone receptors in 126 formalin-fixed, paraffin-embedded melanocytic tumours comprising melanocytic naevi, superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma and metastatic melanomas. The relative proportion of positive cells and intensity of staining was higher in neoplastic cells, compared to normal cutaneous cells. Of the 76 cases of common melanocytic naevi (CMN) studies, 46 were weakly reactive with MAb 263. Heterogeneity of immunoreactivity was found in primary melanoma lesions with a variable range of positive cells. Of 37 cases studied, 34 were moderately to strongly positive. Immunoreactivity showed subcellular localization of the GH-receptor in cell membranes, was predominantly cytoplasmic, but strong nuclear immunoreaction was also apparent in many instances. The nuclear localization of immunoreactivity is the result of nuclear GH-receptor/binding protein, identically to the cytosolic and plasma growth hormone binding protein. Intense immuno-reactivity was also observed in the cellular Golgi area of established cell lines and cultured tissue-derived cells in exponential growth phase, indicating cells are capable of GH-receptor synthesis. In the primary lesions, dermal tumour cells tended to be more immunoreactive relative to those seen in the dermal region. Metastatic lesions in various organs also expressed growth hormone receptors in secondary tumour cells and all of the metastatic cases were positive. The expression of GH-receptors in human melanoma cells means that these cells are directly responsive to GH action and that GH may stimulate local production of IGF-I, which then acts in an autocrine mechanism.
Lincoln
D T
DT
Department of Medical Sciences, Faculty of Allied Health, Kuwait University, Kuwait.
Sinowatz
F
F
Kölle
S
S
Takahashi
H
H
Parsons
P
P
Waters
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000276:immunology; D002462:Cell Membrane / Q000737:chemistry; D002467:Cell Nucleus / Q000737:chemistry; D003600:Cytosol / Q000737:chemistry; D000939:Epitopes / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic; D006056:Golgi Apparatus / Q000737:chemistry; D006801:Humans; D018327:Hutchinson's Melanotic Freckle / Q000737:chemistry / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D015603:Keratinocytes / Q000737:chemistry; D008544:Melanocytes / Q000737:chemistry; D008545:Melanoma / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D009508:Nevus, Pigmented / Q000737:chemistry / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D012867:Skin / Q000737:chemistry; D012878:Skin Neoplasms / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000939:Epitopes; D009363:Neoplasm Proteins; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I