2-Deoxy-L-ribose inhibits the invasion of thymidine phosphorylase-overexpressing tumors by suppressing matrix metalloproteinase-9.
Thymidine phosphorylase (TP), an enzyme involved in pyrimidine metabolism, is identical with an angiogenic factor, platelet-derived endothelial cell growth factor. 2-Deoxy-D-ribose (D-dRib), the degradation product of thymidine generated by TP activity, has been suggested to be a downstream mediator of TP function. 2-Deoxy-L-ribose (L-dRib), a stereoisomer of D-dRib, inhibited the promotion of angiogenesis, tumor growth and metastasis by TP. In our study, we have shown that nude mice inoculated with TP-overexpressing KB/TP cells had shorter survival times than those injected with control KB/CV cells. KB/TP tumors were also more highly invasive than KB/CV tumors in mice. The expression levels of matrix metalloproteinase (MMP)-9 in KB/TP tumors were significantly higher than those in KB/CV tumors. L-dRib and a TP inhibitior, TPI, extended the survival period of KB/TP tumor-bearing mice. L-dRib also reduced MMP-9 mRNA levels in KB/TP tumors. Furthermore, L-dRib suppressed the mRNA level of MMP-9 in cultured KB/TP cells, and the invasive activity of the cells. L-dRib may be useful for the suppression of invasion of TP-expressing tumor cells.
Nakajima
Yuichi
Y
Department of Molecular Oncology, Field of Oncology, Course of Advanced Therapeutics,Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Japan.
Haraguchi
Misako
M
Furukawa
Tatsuhiko
T
Yamamoto
Masatatsu
M
Nakanishi
Hayao
H
Tatematsu
Masae
M
Akiyama
Shin-ichi
S
D000818:Animals; D045744:Cell Line, Tumor; D003470:Culture Media; D003855:Deoxyribose / Q000494:pharmacology*; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control / Q000556:secondary; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control / Q000556:secondary; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D015996:Survival Rate; D013939:Thymidine Phosphorylase / Q000235:genetics / Q000378:metabolism*
D003470:Culture Media; D003855:Deoxyribose; D013939:Thymidine Phosphorylase; D020780:Matrix Metalloproteinase 9