1. Involvement of adrenomedullin induced by hypoxia in angiogenesis in human renal cell carcinoma.
- Author
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Fujita Y, Mimata H, Nasu N, Nomura T, Nomura Y, and Nakagawa M
- Subjects
- Adrenomedullin, Adult, Aged, Aged, 80 and over, Carcinoma, Renal Cell pathology, Female, Humans, Hypoxia pathology, In Vitro Techniques, Kidney drug effects, Kidney Neoplasms pathology, Male, Middle Aged, Neovascularization, Physiologic drug effects, Peptides analysis, Tumor Cells, Cultured drug effects, Tumor Cells, Cultured pathology, Tumor Cells, Cultured physiology, Vasodilator Agents analysis, Carcinoma, Renal Cell blood supply, Carcinoma, Renal Cell physiopathology, Hypoxia physiopathology, Kidney blood supply, Kidney physiopathology, Kidney Neoplasms blood supply, Kidney Neoplasms physiopathology, Neovascularization, Physiologic physiology, Peptides pharmacology, Vasodilator Agents pharmacology
- Abstract
Background: Adrenomedullin (AM) has pluripotent activities and is involved in the regulation of vasomotor tone, cell differentiation and embryogenesis. However, the expression and pathophysiological role of AM has not been determined in human renal cell carcinoma (RCC)., Methods: Twenty-six RCC specimens and three cultured human RCC cell lines (A498, SN12C and KPK-13) were analyzed. Expression of AM was determined by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) analysis. The correlation between AM expression and microvessel count (MVC) in RCC specimens was examined to determine if AM plays a role in tumor angiogenesis. The correlation between the expression of AM and vascular endothelial growth factor (VEGF) was also investigated. Lastly, the effect of hypoxia upon the mRNA expression of AM, VEGF and hypoxia inducible factor-1 (HIF-1) by RCC cell lines was determined., Results: Immunohistochemistry indicated that AM and VEGF were primarily localized in the cytosol of RCC cells. AM and VEGF mRNA were detected in all RCC specimens and cultured RCC cell lines analyzed by RT-PCR. There was a positive correlation between AM mRNA expression and MVC (r = 0.516, P = 0.0062), and between VEGF mRNA expression and MVC (r = 0.485, P = 0.0111). We also observed a positive correlation between AM mRNA expression and VEGF mRNA expression (r = 0.552, P = 0.0029). Hypoxia significantly induced AM and VEGF mRNA expression, although the increase of the AM mRNA level (10.6-26.7 fold) was markedly greater than that of the VEGF mRNA level (1.5-1.9 fold)., Conclusion: These results suggest that hypoxia-induced AM plays a part in tumor angiogenesis in conjunction with VEGF and facilitates human RCC growth under hypoxic conditions.
- Published
- 2002
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