Investigators at Soochow University, Department of General Surgery target angiogenesis
December 29th, 2008
2008 DEC 29 -- A new study, 'Effect of endothelial PAS domain protein 1 and hypoxia inducible factor 1alpha on vascular endothelial growth factor expression in human pancreatic carcinoma,' is now available. "Transcription factors hypoxia inducible factor 1alpha (HIF 1alpha) and endothelial PAS domain protein 1 (EPAS1) promote the transcription of vascular endothelial growth factor (VEGF). VEGF enhances angiogenesis and vascular permeability of tumours, which promotes tumor growth and facilitates entry of cancer cells into blood circulation and metastasizing," scientists in Suzhou, People's Republic of China report.
"This study examined whether HIF 1alpha and EPAS1 stimulated angiogenesis through activation of VEGF in human pancreatic carcinoma. Specimens from pancreatic carcinoma and healthy parts of same pancreas were taken from 60 patients. Real time quantitative reverse transcription polymerase chain reaction estimated expression of HIF 1alpha, EPAS1, and VEGF mRNAs. Western blotting and immunohistochemical, streptavidin peroxidase method assessed expression of HIF 1alpha, EPAS1, and VEGF proteins. Microvessel density (MVD) was assessed. Highly significant increases in expression of EPAS1, VEGF, and MVD were found in pancreatic carcinoma tissue but not in normal pancreatic tissue: VEGF at mRNA and protein levels (t=17.32, p=0.0001; t=98.41, p=0.0001); EPAS1 protein level (t=22.51, p=0.0001). Expression of HIF 1alpha was similar in pancreatic carcinoma and normal pancreatic tissues at both mRNA and protein levels. Significant correlations were observed between EPAS1 and VEGF (r=0.736, p=0.0041), between VEGF and MVD (r=0.858, p=0.0001), and between EPAS1 and MVD (r=0.641, p=0.0003). No significant correlations were observed between HIF 1alpha and VEGF, or between HIF 1alpha and MVD. MVD and expression of EPAS1 and VEGF were significantly related with TNM staging, so was EPASI and VEGF with size of tumour. EPAS1 and VEGF, but not HIF1alpha, are overexpressed in pancreatic carcinoma. The expression of EPAS1 is correlated with that of VEGF and MVD. EPAS1 may be involved in the angiogenesis of pancreatic carcinoma by upregulating the expression of VEGF," wrote D.M. Zhu and colleagues, Soochow University, Department of General Surgery.
The researchers concluded: "Targeting EPAS1 may be a new method of antiangiogenic tumor therapy for pancreatic carcinoma."
Zhu and colleagues published their study in Chinese Medical Journal (Effect of endothelial PAS domain protein 1 and hypoxia inducible factor 1alpha on vascular endothelial growth factor expression in human pancreatic carcinoma. Chinese Medical Journal, 2008;121(22):2258-64).
For additional information, contact D.M. Zhu, First Affiliated Hospital of Soochow University, Dept. of General Surgery, Suzhou, Jiangsu 215006, China.
The publisher's contact information for the Chinese Medical Journal is: Chinese Medical Association, 42 Dongsi Xidajie, Beijing 100710, People's Republic of China.
