Angiogenic factor

Furukawa, Tatsuhiko; Yoshimura, Akihiko; Sumizawa, Tomoyuki; Haraguchi, Masanobu; Akiyama, S; Fukui, Kiyoshi; Ishizawa, Minoru; Yamada, Yuji

doi:10.1038/356668a0

Cited by 319 publications

(178 citation statements)

References 4 publications

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“…Recently, several angiogenic factors have been identified and PD-ECGF is thought to be one such factor (Ishikawa et al, 1989;Furukawa et al, 1992;Toi et al, 1994). Ishikawa et al (1989 and Usuki et al (1992) reported that PD-ECGF stimulates the growth and chemotaxis of endothelial cells in vitro and possesses angiogenic activity in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…However, there have been few studies on the correlation between the expression of angiogenic factors and progression of malignant tumours. Recently, it was reported that thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECGF), which is thought to be an angiogenic factor (Ishikawa et al, 1989;Furukawa et al, 1992;Haraguchi et al, 1994).…”

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confidence: 99%

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Thymidine phosphorylase/platelet-derived endothelial cell growth factor expression associated with hepatic metastasis in gastric carcinoma

Maeda

Chung²,

Ogawa³

et al. 1996

Br J Cancer

138

108

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Summary It is known that angiogenesis plays an important role in the growth and metastasis of solid tumours. Several angiogenic factors have been identified and platelet-derived endothelial cell growth factor (PD-ECGF) is thought to be one such factor. Recently, it was reported that thymidine phosphorylase (dThdPase) is identical to PD-ECGF. Using immunohistochemical staining with an anti-dThdPase antibody, we investigated the correlation between dThdPase expression and the microvessel density in 120 gastric carcinomas. The microvessel density, determined by immunostaining for factor VIII-related antigen, was significantly higher in dThdPase-positive tumours than in dThdPase-negative tumours. There was a significant correlation between dThdPase expression and the increment of microvessel density. Moreover, regarding distant organ metastasis, the frequency of hepatic metastasis was significantly higher (P<0.01) in patients with dThdPase-positive tumours than in those with dThdPase-negative tumours. In summary, it was suggested that dThdPase expression is closely associated with the promotion of angiogenesis and hepatic metastasis in gastric carcinoma.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Thymidine phosphorylase/platelet-derived endothelial cell growth factor expression associated with hepatic metastasis in gastric carcinoma

Maeda

Chung²,

Ogawa³

et al. 1996

Br J Cancer

138

108

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“…Sequence analysis of the gene revealed a stretch of 120 amino acids to be identical to thymidine phosphorylase (TP), an enzyme catalysing the reversible phosphorolysis of thymidine to thymine and 2-deoxyribose-1-phosphate (dR-1-P) (Furukawa et al, 1992). Subsequently, this enzymatic activity was identified for PD-ECGF (Moghaddam and Bicknell, 1992;Usuki et al, 1992).…”

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confidence: 99%

Role of platelet-derived endothelial cell growth factor/thymidine phosphorylase in fluoropyrimidine sensitivity

et al. 2003

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Platelet-derived endothelial cell growth factor (PD-ECGF)/thymidine phosphorylase (TP) catalyses the reversible phosphorolysis of thymidine to thymine and 2-deoxyribose-1-phosphate and is involved in the metabolism of fluoropyrimidines. It can also activate 5 0 -deoxyfluorouridine (5 0 DFUR) and possibly 5-fluorouracil (5FU) and Ftorafur (Ft), but inactivates trifluorothymidine (TFT). We studied the contribution of TP activity to the sensitivity for these fluoropyrimidines by modulating its activity and/or expression level in colon and lung cancer cells using a specific inhibitor of TP (TPI) or by overproduction of TP via stable transfection of human TP. Expression was analysed using competitive template-RT -PCR (CT-RT -PCR), Western blot and an activity assay. TP activity ranged from nondetectable to 70678 pmol h À1 10 À6 cells, in Colo320 and a TP overexpressing clone Colo320TP1, respectively. We found a good correlation between TP activity and mRNA expression (r ¼ 0.964, Po0.01) in our cell panel. To determine the role of TP in the sensitivity to 5FU, 5 0 DFUR, Ft and TFT, cells were cultured with the various fluoropyrimidines with or without TPI and differences in IC 50 's were established. TPI modified 5 0 DFUR, increasing the IC 50 's 2.5-to 1396-fold in WiDR and Colo320TP1, respectively. 5-Fluorouracil could be modified by inhibiting TP but to a lesser extent than 5 0 DFUR: IC 50 's increased 1.9-to 14.7-fold for WiDR and Colo320TP1, respectively. There was no effect on TFT or Ft. There appears to be a threshold level of TP activity to influence the 5 0 DFUR and 5FU sensitivity, which is higher for 5FU. Even high levels of TP overexpression only had a moderate effect on 5FU sensitivity.

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“…It was reported as both chemotactic and mitogenic for endothelial cells and angiogenic in several model systems (Ishikawa et al, 1989;Haraguchi et al, 1994;Moghaddam et al, 1995). However, recently PD-ECGF has been shown to be thymidine phosphorylase (TP) (Barton et al, 1992;Furukawa et al, 1992;Moghaddam and Bicknell, 1992;Usuki et al, 1992;Finnis et al, 1993;Sumizawa et al, 1993). TP catalyses the reversible phosphorolysis of thymidine to deoxyribose 1-phosphate and thymine.…”

mentioning

confidence: 99%

The angiogenic factor platelet-derived endothelial cell growth factor/thymidine phosphorylase is up-regulated in breast cancer epithelium and endothelium

Fox

Westwood²,

Moghaddam³

et al. 1996

Br J Cancer

140

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Summary Tumour angiogenesis is a complex multistep process regulated by a number of angiogenic factors. One such factor, platelet-derived endothelial cell growth factor has recently been shown to be thymidine phosphorylase (TP). TP catalyses the reversible phosphorylation of thymidine to deoxyribose-1 -phosphate and thymine. Although known to be generally elevated in tumours, the expression of this enzyme in breast carcinomas is unknown. Therefore, we used ribonuclease protection assays and immunohistochemistry to examine the expression of TP in 240 primary breast carcinomas. Nuclear and/or cytoplasmic TP expression was observed in the neoplastic tumour epithelium in 53% of tumours. Immunoreactivity was also often present in the stromal, inflammatory and endothelial cell elements. Although endothelial cell staining was usually focal, immunoreactivity was observed in 61 % of tumours and was prominent at the tumour periphery, an area where tumour angiogenesis is most active. Tumour cell TP expression was significantly inversely correlated with grade (P = 0.05) and size (P = 0.003) but no association was observed with other tumour variables. These findings suggest that TP is important for remodelling the existing vasculature early in tumour development, consistent with its chemotactic non-mitogenic properties, and that additional angiogenic factors are more important for other angiogenic processes like endothelial cell proliferation. Relapse-free survival was higher in node-positive patients with elevated TP (P = 0.05) but not in other patient groups. This might be due to the potentiation of chemotherapeutic agents like methotrexate by TP. Therefore, this enzyme might be a prediction marker for response to chemotherapy.

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Angiogenic factor

Cited by 319 publications

References 4 publications

Thymidine phosphorylase/platelet-derived endothelial cell growth factor expression associated with hepatic metastasis in gastric carcinoma

Thymidine phosphorylase/platelet-derived endothelial cell growth factor expression associated with hepatic metastasis in gastric carcinoma

Role of platelet-derived endothelial cell growth factor/thymidine phosphorylase in fluoropyrimidine sensitivity

The angiogenic factor platelet-derived endothelial cell growth factor/thymidine phosphorylase is up-regulated in breast cancer epithelium and endothelium

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