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. 1999 Mar;79(7-8):1145–1150. doi: 10.1038/sj.bjc.6690182

Thymidine phosphorylase/platelet-derived endothelial cell growth factor is upregulated in advanced solid types of gastric cancer

T Yoshikawa 1, K Suzuki 1, O Kobayashi 1, M Sairenji 1, H Motohashi 1, A Tsuburaya 1, Y Nakamura 2, A Shimizu 2, S Yanoma 3, Y Noguchi 4
PMCID: PMC2362246  PMID: 10098749

Abstract

Previous studies demonstrated that the immunohistochemical expression of thymidine phosphorylase (dThdPase) was related with distant metastasis and disease progression. In this study we investigated the production of dThdPase/platelet-derived endothelial cell growth factor in gastric cancer quantitatively. In a total of 75 tumour tissues and 60 normal gastric mucosa specimens, dThdPase protein concentrations were determined by ELISA. The amount of dThdPase was significantly higher in the tumour tissue than in the normal tissue. Intratumoural dThdPase concentrations were significantly higher in Borrmann types I and II macroscopically, in poorly differentiated and solid type histologically, in the medullary type of the tumour stroma, and in the tumour-invading serosa. In the medullary type of the amount of tumour stroma, protein levels of dThdPase were positively correlated with the vertical diameter of the tumour (r = 0.580, P = 0.019). By immunohistochemical study, dThdPase expression on tumour cells was observed in all seven specimens with high dThdPase protein levels, but not in all 14 cases with low dThdPase protein levels (P < 0.05). In summary, these data indicated that dThdPase is up-regulated in advanced solid types of gastric cancer, suggesting that dThdPase production in carcinoma cells might be induced by the microenvironment. © 1999 Cancer Research Campaign

Keywords: thymidine phosphorylase, platelet-derived endothelial cell growth factor, gastric carcinoma

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Selected References

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  1. Cook A. F., Holman M. J., Kramer M. J., Trown P. W. Fluorinated pyrimidine nucleosides. 3. Synthesis and antitumor activity of a series of 5'-deoxy-5-fluoropyrimidine nucleosides. J Med Chem. 1979 Nov;22(11):1330–1335. doi: 10.1021/jm00197a010. [DOI] [PubMed] [Google Scholar]
  2. Eda H., Fujimoto K., Watanabe S., Ura M., Hino A., Tanaka Y., Wada K., Ishitsuka H. Cytokines induce thymidine phosphorylase expression in tumor cells and make them more susceptible to 5'-deoxy-5-fluorouridine. Cancer Chemother Pharmacol. 1993;32(5):333–338. doi: 10.1007/BF00735915. [DOI] [PubMed] [Google Scholar]
  3. Folkman J., Klagsbrun M. Angiogenic factors. Science. 1987 Jan 23;235(4787):442–447. doi: 10.1126/science.2432664. [DOI] [PubMed] [Google Scholar]
  4. Fox S. B., Westwood M., Moghaddam A., Comley M., Turley H., Whitehouse R. M., Bicknell R., Gatter K. C., Harris A. L. The angiogenic factor platelet-derived endothelial cell growth factor/thymidine phosphorylase is up-regulated in breast cancer epithelium and endothelium. Br J Cancer. 1996 Feb;73(3):275–280. doi: 10.1038/bjc.1996.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Furukawa T., Yoshimura A., Sumizawa T., Haraguchi M., Akiyama S., Fukui K., Ishizawa M., Yamada Y. Angiogenic factor. Nature. 1992 Apr 23;356(6371):668–668. doi: 10.1038/356668a0. [DOI] [PubMed] [Google Scholar]
  6. Griffiths L., Dachs G. U., Bicknell R., Harris A. L., Stratford I. J. The influence of oxygen tension and pH on the expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in human breast tumor cells grown in vitro and in vivo. Cancer Res. 1997 Feb 15;57(4):570–572. [PubMed] [Google Scholar]
  7. Griffiths L., Stratford I. J. Platelet-derived endothelial cell growth factor thymidine phosphorylase in tumour growth and response to therapy. Br J Cancer. 1997;76(6):689–693. doi: 10.1038/bjc.1997.447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ishikawa F., Miyazono K., Hellman U., Drexler H., Wernstedt C., Hagiwara K., Usuki K., Takaku F., Risau W., Heldin C. H. Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor. Nature. 1989 Apr 13;338(6216):557–562. doi: 10.1038/338557a0. [DOI] [PubMed] [Google Scholar]
  9. Ishitsuka H., Miwa M., Takemoto K., Fukuoka K., Itoga A., Maruyama H. B. Role of uridine phosphorylase for antitumor activity of 5'-deoxy-5-fluorouridine. Gan. 1980 Feb;71(1):112–123. [PubMed] [Google Scholar]
  10. Kono A., Hara Y., Sugata S., Karube Y., Matsushima Y., Ishitsuka H. Activation of 5'-deoxy-5-fluorouridine by thymidine phosphorylase in human tumors. Chem Pharm Bull (Tokyo) 1983 Jan;31(1):175–178. doi: 10.1248/cpb.31.175. [DOI] [PubMed] [Google Scholar]
  11. Maeda K., Chung Y. S., Ogawa Y., Takatsuka S., Kang S. M., Ogawa M., Sawada T., Onoda N., Kato Y., Sowa M. Thymidine phosphorylase/platelet-derived endothelial cell growth factor expression associated with hepatic metastasis in gastric carcinoma. Br J Cancer. 1996 Apr;73(8):884–888. doi: 10.1038/bjc.1996.177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Miyazono K., Okabe T., Urabe A., Takaku F., Heldin C. H. Purification and properties of an endothelial cell growth factor from human platelets. J Biol Chem. 1987 Mar 25;262(9):4098–4103. [PubMed] [Google Scholar]
  13. Nio Y., Kimura H., Tsubono M., Tseng C. C., Kawabata K., Masai Y., Hayashi H., Meyer C., Fukumoto M., Tobe T. Antitumor activity of 5'-deoxy-5-fluorouridine in human digestive organ cancer xenografts and pyrimidine nucleoside phosphorylase activity in normal and neoplastic tissues from human digestive organs. Anticancer Res. 1992 Jul-Aug;12(4):1141–1146. [PubMed] [Google Scholar]
  14. Nishida M., Hino A., Mori K., Matsumoto T., Yoshikubo T., Ishitsuka H. Preparation of anti-human thymidine phosphorylase monoclonal antibodies useful for detecting the enzyme levels in tumor tissues. Biol Pharm Bull. 1996 Nov;19(11):1407–1411. doi: 10.1248/bpb.19.1407. [DOI] [PubMed] [Google Scholar]
  15. Takebayashi Y., Miyadera K., Akiyama S., Hokita S., Yamada K., Akiba S., Yamada Y., Sumizawa T., Aikou T. Expression of thymidine phosphorylase in human gastric carcinoma. Jpn J Cancer Res. 1996 Mar;87(3):288–295. doi: 10.1111/j.1349-7006.1996.tb00219.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Takebayashi Y., Yamada K., Miyadera K., Sumizawa T., Furukawa T., Kinoshita F., Aoki D., Okumura H., Yamada Y., Akiyama S. The activity and expression of thymidine phosphorylase in human solid tumours. Eur J Cancer. 1996 Jun;32A(7):1227–1232. doi: 10.1016/0959-8049(96)00061-5. [DOI] [PubMed] [Google Scholar]
  17. Yoshimura A., Kuwazuru Y., Furukawa T., Yoshida H., Yamada K., Akiyama S. Purification and tissue distribution of human thymidine phosphorylase; high expression in lymphocytes, reticulocytes and tumors. Biochim Biophys Acta. 1990 Apr 23;1034(1):107–113. doi: 10.1016/0304-4165(90)90160-x. [DOI] [PubMed] [Google Scholar]

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