Effects of Platelet-derived Endothelial Cell Growth Factor/thymidine Phosphorylase, Substrate, and Products in a Three-dimensional Model of Angiogenesis

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 1998 Jun 17

PMID 9626068

Citations 9

Authors

D P Stevenson

S R Milligan

W P COLLINS

Affiliations

Soon will be listed here.

Abstract

Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) is associated with angiogenesis and the progression of human breast and ovarian cancers. The aim of this study was to obtain information about the possible mechanisms of PD-ECGF/TP activity in an established three-dimensional model of angiogenesis. The plan was to study the effects of the enzyme, substrate, products, and further metabolites on the formation and rate of microvessel growth from cultured segments of rat aorta in serum-free media. The end-points were the number and length of microvessels compared with controls after 4, 7, 11, and 14 days in culture. Thymidine (10 to 1000 mumol/L), thymidine-5'-monophosphate (1000 mumol/L), and 2'-deoxy-D-ribose-1-phosphate (1000 mumol/L) inhibited the number of microvessels produced. Conversely PD-ECGF/TP (50 to 100 ng/ml) and beta-amino-iso-butyric acid (1000 mumol/L--a metabolite of thymine) had a significant stimulatory effect (P < 0.05, P < 0.01, P < 0.001 respectively on culture day 11). PD-ECGF (10 ng/ml), beta-amino-iso-butyric acid (1000 mumol/L), and 2-deoxy-D-ribose (100 to 1000 mumol/L) significantly (P < 0.001, P < 0.01, P < 0.01, respectively) stimulated microvessel elongation by day 11. We conclude that PD-ECGF/TP may affect angiogenesis by changing the relative concentrations of pyrimidine-based compounds and their metabolites in interstitial fluid surrounding endothelial cells. Drugs that inhibit PD-ECGF/TP activity may therefore delay abnormal angiogenesis and the progression of various cancers.

Citing Articles

Protective autophagy by thymidine causes resistance to rapamycin in colorectal cancer cells .

Bijnsdorp I, Peters G Cancer Drug Resist. 2022; 4(3):719-727.

PMID: 35582304 PMC: 9094079. DOI: 10.20517/cdr.2021.21.

Basic Research on Tendon Repair: Strategies, Evaluation, and Development.

Li Z, Yang Q, Zhou Y Front Med (Lausanne). 2021; 8:664909.

PMID: 34395467 PMC: 8359775. DOI: 10.3389/fmed.2021.664909.

The effect of butyric acid with autogenous omental graft on healing of experimental Achilles tendon injury in rabbits.

Jahani S, Moslemi H, Dehghan M, Sedaghat R, Mazaheri Nezhad R, Rezaee Moghaddam D Iran J Vet Res. 2016; 16(1):100-4.

PMID: 27175160 PMC: 4789249.

Thymidine phosphorylase in cancer cells stimulates human endothelial cell migration and invasion by the secretion of angiogenic factors.

Bijnsdorp I, Capriotti F, Kruyt F, Losekoot N, Fukushima M, Griffioen A Br J Cancer. 2011; 104(7):1185-92.

PMID: 21386840 PMC: 3068508. DOI: 10.1038/bjc.2011.74.

The dual role of thymidine phosphorylase in cancer development and chemotherapy.

Bronckaers A, Gago F, Balzarini J, Liekens S Med Res Rev. 2009; 29(6):903-53.

PMID: 19434693 PMC: 7168469. DOI: 10.1002/med.20159.

References

Furukawa T, Yoshimura A, Sumizawa T, Haraguchi M, Akiyama S, Fukui K . Angiogenic factor. Nature. 1992; 356(6371):668. DOI: 10.1038/356668a0. View

Nicosia R, Ottinetti A . Growth of microvessels in serum-free matrix culture of rat aorta. A quantitative assay of angiogenesis in vitro. Lab Invest. 1990; 63(1):115-22. View

Usuki K, Saras J, Waltenberger J, Miyazono K, Pierce G, Thomason A . Platelet-derived endothelial cell growth factor has thymidine phosphorylase activity. Biochem Biophys Res Commun. 1992; 184(3):1311-6. DOI: 10.1016/s0006-291x(05)80025-7. View

Folkman J, Shing Y . Angiogenesis. J Biol Chem. 1992; 267(16):10931-4. View

Moghaddam A, Bicknell R . Expression of platelet-derived endothelial cell growth factor in Escherichia coli and confirmation of its thymidine phosphorylase activity. Biochemistry. 1992; 31(48):12141-6. DOI: 10.1021/bi00163a024. View

Nicosia R, Bonanno E, Smith M . Fibronectin promotes the elongation of microvessels during angiogenesis in vitro. J Cell Physiol. 1993; 154(3):654-61. DOI: 10.1002/jcp.1041540325. View

Finnis C, Dodsworth N, Pollitt C, Carr G, Sleep D . Thymidine phosphorylase activity of platelet-derived endothelial cell growth factor is responsible for endothelial cell mitogenicity. Eur J Biochem. 1993; 212(1):201-10. DOI: 10.1111/j.1432-1033.1993.tb17651.x. View

Barton G, Ponting C, Spraggon G, Finnis C, Sleep D . Human platelet-derived endothelial cell growth factor is homologous to Escherichia coli thymidine phosphorylase. Protein Sci. 1992; 1(5):688-90. PMC: 2142224. DOI: 10.1002/pro.5560010514. View

Sumizawa T, Furukawa T, Haraguchi M, Yoshimura A, Takeyasu A, Ishizawa M . Thymidine phosphorylase activity associated with platelet-derived endothelial cell growth factor. J Biochem. 1993; 114(1):9-14. DOI: 10.1093/oxfordjournals.jbchem.a124146. View

10.

Haraguchi M, Miyadera K, Uemura K, Sumizawa T, Furukawa T, Yamada K . Angiogenic activity of enzymes. Nature. 1994; 368(6468):198. DOI: 10.1038/368198a0. View

11.

Reynolds K, Farzaneh F, COLLINS W, Campbell S, Bourne T, Lawton F . Association of ovarian malignancy with expression of platelet-derived endothelial cell growth factor. J Natl Cancer Inst. 1994; 86(16):1234-8. DOI: 10.1093/jnci/86.16.1234. View

12.

Moghaddam A, Zhang H, Fan T, Hu D, Lees V, Turley H . Thymidine phosphorylase is angiogenic and promotes tumor growth. Proc Natl Acad Sci U S A. 1995; 92(4):998-1002. PMC: 42624. DOI: 10.1073/pnas.92.4.998. View

13.

Miyadera K, Sumizawa T, Haraguchi M, Yoshida H, Konstanty W, Yamada Y . Role of thymidine phosphorylase activity in the angiogenic effect of platelet derived endothelial cell growth factor/thymidine phosphorylase. Cancer Res. 1995; 55(8):1687-90. View

14.

Gruber B, Marchese M, Kew R . Angiogenic factors stimulate mast-cell migration. Blood. 1995; 86(7):2488-93. View

15.

Folkman J . Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995; 1(1):27-31. DOI: 10.1038/nm0195-27. View

16.

Jaggers D, COLLINS W, Milligan S . Potent inhibitory effects of steroids in an in vitro model of angiogenesis. J Endocrinol. 1996; 150(3):457-64. DOI: 10.1677/joe.0.1500457. View

17.

BERLIN R, Oliver J . Membrane transport of purine and pyrimidine bases and nucleosides in animal cells. Int Rev Cytol. 1975; 42:287-336. DOI: 10.1016/s0074-7696(08)60983-3. View

18.

Maca R, Fry G, HOAK J, Loh P . The effects of intact platelets on cultured human endothelial cells. Thromb Res. 1977; 11(6):715-27. DOI: 10.1016/0049-3848(77)90100-1. View

19.

Wohlhueter R, Marz R, Plagemann P . Thymidine transport in cultured mammalian cells. Kinetic analysis, temperature dependence and specificity of the transport system. Biochim Biophys Acta. 1979; 553(2):262-83. DOI: 10.1016/0005-2736(79)90231-1. View

20.

ODwyer P, King S, Hoth D, Leyland-Jones B . Role of thymidine in biochemical modulation: a review. Cancer Res. 1987; 47(15):3911-9. View