1994 Fiscal Year Final Research Report Summary
The mechanism of angiogenesis by PD-ECGF
| Project/Area Number |
05044182
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Kagoshima University |
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Principal Investigator |
AKIYAMA Shin-ichi Professor, Faculty of Medicine, Kagoshima University, 医学部, 教授 (60117413)
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| Co-Investigator(Kenkyū-buntansha) |
PIRKER Robert Associate Professor, University of Vienna, Medical School, 医学部, 助教授
MIYAZONO Kohei Group leader, Ludwig Institute for Cancer Research, Uppsala Branch, ウプサラ支部, グループリーダー
HELDIN Carlー ルードヴィヒ癌研究所, ウプサラ支部, 所長
HARAGUCHI Misako Instructor, Faculty of Medicine, Kagoshima University, 医学部, 助手 (10244229)
SUMIZAWA Tomoyuki Instructor, Faculty of Medicine, Kagoshima University, 医学部, 助手 (90206582)
YOSHIMURA Akihiko Associate Professor, Faculty of Medicine, Kagoshima University, 医学部, 助教授 (90182815)
HELDIN Carl-henrich Director, Ludwig Institute for Cancer Research, Uppsala Branch
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| Project Period (FY) |
1993 – 1994
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| Keywords | Thymidine Phosphorylase / PD-ECGF / Angiogenic factor / Deoxyribose / Colorectal carcinoma / Thrombomodulin / Metastasis / Prognosis |
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| Research Abstract |
Human thymidine phosphorylase (dThdPase) has been reported to be identical with the platelet derived endothelial cell growth factor (PD-ECGF). To investigate whether the dThdPase activity of PD-ECGF/dThdPase is indispensable to its angiogenic activity, three PD-ECGF/dThdPase mutants, K115E (Lys-115*Glu mutant) , L148R (Leu-148*Arg mutant) and R202S (Arg-202*Ser mutant) were made by site-directed mutagenesis. Although the expression level of the three mutant PD-ECGF/dThdPase in COS cells was similar to that of wild type PD-ECGF/dThdPase, dThdPase activity was not detected in the COS-7 cells transfected with the mutant PD-ECGF/dThdPase cDNAs. The lysates of COS-7 cells transfected with the wild-type PD-ECGF/dThdPase cDNA had angiogenic activity but that transfected with the mutant PD-ECGF/dThdPase cDNA did not. These findings indicate that dThdPase activity is indispensable to the anigogenic activity of PD-ECGF/dThdPase.
dThdPase activity is increased in several types of malignant tumors.
… More
We measured the dThdPase activity and the level of thrombomodulin (TM) , as a marker for endothelial cells, in colorectal carcinomas and adjacent normal tissues from 21 patients, and in adenomas from 13 patients. The average dThdPase activity of colorectal carcinomas was significantly higher than that of adenomas or normal tissues. In immunohistochemical study, the expression of dThdPase was observed more frequently in colorectal carcinomas than in adenomas or normal mucosas. The amount of TM in colorectal carcinomas was significantly higher than that of adenomas or normal tissue. dThdPase activity in human colorectal carcinomas, adenomas and normal tissues was significantly correlated with the expression of TM in these tissues. These results indicate that the expression levels of both dThdPase and TM in colorectal carcinomas are higher than those in colorectal adenomas and normal tissues, and dThdPase may be involved in angiogenesis in human colorectal carcinomas, adenomas and normal tissues. Less
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