Accumulation of thymidine-derived sugars in thymidine phosphorylase overexpressing cells

Bijnsdorp, Irene V.; Azijli, Kaamar; Jansen, Erwin E.W.; Wamelink, Mirjam M. C.; Jakobs, Cornelis; Struys, Eduard A.; Fukushima, Masakazu; Kruyt, Frank A.E.; Peters, Godefridus J.

doi:10.1016/j.bcp.2010.05.009

Cited by 31 publications

(30 citation statements)

References 40 publications

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“…It is known that many tumour cells generate relatively large mounts of deoxyribose (Bjinsdorp et al, 2008(Bjinsdorp et al, , 2010(Bjinsdorp et al, , 2011, resulting from upregulated thymidine phosphorylase activity which generally characterises many cancer cells; deoxyribose confers resistance to apoptosis (Ikeda et al, 2006;Nakajima et al, 2006). Carnosine can react with deoxyribose however (Hipkiss et al, 1995).…”

Section: Carnosine and Tumoursmentioning

confidence: 99%

Energy metabolism, proteotoxic stress and age-related dysfunction – Protection by carnosine

Hipkiss

2011

Molecular Aspects of Medicine

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Section: Carnosine and Tumoursmentioning

confidence: 99%

Energy metabolism, proteotoxic stress and age-related dysfunction – Protection by carnosine

Hipkiss

2011

Molecular Aspects of Medicine

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mentioning

confidence: 99%

“…From this reaction, deoxyribose (dR) can be formed (Bijnsdorp et al , 2010a). It is believed that dR has a role in the angiogenic effects of TP (Hotchkiss et al , 2003), as dR can be secreted from the cells (Bijnsdorp et al , 2010a). Deoxyribose has shown angiogenic properties in various in vitro and in vivo studies (Stevenson et al , 1998; Hotchkiss et al , 2003; Sengupta et al , 2003).…”

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confidence: 99%

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

et al. 2011

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Background:Thymidine phosphorylase (TP) is often overexpressed in tumours and has a role in tumour aggressiveness and angiogenesis. Here, we determined whether TP increased tumour invasion and whether TP-expressing cancer cells stimulated angiogenesis.Methods:Angiogenesis was studied by exposing endothelial cells (HUVECs) to conditioned medium (CM) derived from cancer cells with high (Colo320TP1=CT-CM, RT112/TP=RT-CM) and no TP expression after which migration (wound-healing-assay) and invasion (transwell-assay) were determined. The involvement of several angiogenic factors were examined by RT–PCR, ELISA and blocking antibodies.Results:Tumour invasion was not dependent on intrinsic TP expression. The CT-CM and RT-CM stimulated HUVEC-migration and invasion by about 15 and 40%, respectively. Inhibition by 10 μ TPI and 100 μ L-dR, blocked migration and reduced the invasion by 50–70%. Thymidine phosphorylase activity in HUVECs was increased by CT-CM. Reverse transcription-polymerase chain reaction revealed a higher mRNA expression of bFGF (Colo320TP1), IL-8 (RT112/TP) and TNF-α, but not VEGF. Blocking antibodies targeting these factors decreased the migration and invasion that was induced by the CT-CM and RT-CM, except for IL-8 in CT-CM and bFGF in RT-CM.Conclusion:In our cell line panels, TP did not increase the tumour invasion, but stimulated the migration and invasion of HUVECs by two different mechanisms. Hence, TP targeting seems to provide a potential additional strategy in the field of anti-angiogenic therapy.

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“…Bijnsdorp et al reported that DR, one of the thymidinederived sugars, is extensively secreted from TP-overexpressing cells (13). When KB/CV cells were incubated in conditioned medium of KB/TP cells (TPCM), expression level of IL-8 mRNA in KB/CV cells was significantly increased (Fig.…”

Section: Tp Activity Is Needed For the Enhanced Expression Of Il-8mentioning

confidence: 92%

“…Thymidine-derived DR and deoxy-d-ribose 1-phosphate (DR1P) are enzymatically converted to 2-deoxy-d-ribose 5-phosphate (DR5P) (12). Bijnsdorp et al observed that DR1P and DR5P accumulate at high levels in TP-overexpressing cells and DR is extensively secreted by these cells (13).…”

Section: Introductionmentioning

confidence: 99%

Thymidine phosphorylase enhances reactive oxygen species generation and interleukin-8 expression in human cancer cells

et al. 2012

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Abstract. Thymidine phosphorylase (TP) is an angiogenic factor that plays a pivotal role in tumor angiogenesis. Various kinds of solid tumors express TP and high TP activity is correlated with microvessel density. We have previously reported that TP enhances interleukin-8 (IL-8) expression in KB human epidermoid carcinoma cells. In this study, TP was shown to be involved in enhanced expression of IL-8 in EJ human bladder cancer cells and Yumoto human cervical cancer cells as well as KB human epidermoid carcinoma cells. The enzymatic activity of TP was required for the enhanced expression of IL-8. A degradation product of thymidine was implicated in the enhanced expression of IL-8. TP augmented reactive oxygen species (ROS) generation in KB and Yumoto cells, and the enzymatic activity of TP was again required for the generation of ROS. An antioxidant, N-acetylcysteine (NAC), attenuated the generation of ROS and IL-8 mRNA expression in KB and Yumoto cells, and H 2 O 2 increased IL-8 mRNA expression in Yumoto cells, suggesting that ROS generated by TP caused the increased expression of IL-8 mRNA. Since TP also reduced cellular glutathione levels and transcription of γ-GCS in KB cells, the TP-induced augmentation of ROS may be partially attributed to the decreased glutathione. Our findings suggest that thymidine-derived sugars enhanced ROS generation and consequently increased IL-8 expression.

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Accumulation of thymidine-derived sugars in thymidine phosphorylase overexpressing cells

Cited by 31 publications

References 40 publications

Energy metabolism, proteotoxic stress and age-related dysfunction – Protection by carnosine

Energy metabolism, proteotoxic stress and age-related dysfunction – Protection by carnosine

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

Thymidine phosphorylase enhances reactive oxygen species generation and interleukin-8 expression in human cancer cells

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