Biological role of thymidine phosphorylase in human astrocytic tumors.
Thymidine phosphorylase (TP) has strong angiogenic activity and is overexpressed in a wide variety of malignant tumors. To elucidate the role of TP in human astrocytic tumors, we immunohistochemically investigated the expression of TP in 62 astrocytic tumors (12 astrocytomas, 12 anaplastic astrocytomas and 38 glioblastomas). Fifty-five astrocytic tumors (88.7%) were immunopositive for TP. The level of TP-expression was significantly correlated with the malignancy grade of astrocytic tumors; most of malignant gliomas highly expressed TP, while a small number of cells were positive in low grade astrocytomas (p < 0.001). Using double-immunostaining, we clarified that TP-expression was predominantly detectable in macrophages. There was no significant correlation between MIB-1 labeling index and TP-expression. However, TP-expression and the microvessel density were well correlated. These suggest that TP, mainly produced by the infiltrated macrophages, may play an important role in the progression of astrocytic tumors via neovascularization. Inhibitor of TP may represent a therapeutic modality for treating malignant gliomas.
Tanioka
K
K
Department of Neurosurgery, Faculty of Medicine, Kagoshima University, Kagoshima 890-8520, Japan. tanioka@med1.kufm.kagoshima-u.ac.jp
Takeshima
H
H
Hirano
H
H
Kimura
T
T
Nagata
S
S
Akiyama
S
S
Kuratsu
J
J
D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D034961:Antigens, Nuclear; D001254:Astrocytoma / Q000098:blood supply / Q000201:enzymology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000098:blood supply / Q000201:enzymology; D049452:Green Fluorescent Proteins; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen; D008164:Luminescent Proteins / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008833:Microcirculation / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000201:enzymology*; D009687:Nuclear Proteins / Q000378:metabolism; D013939:Thymidine Phosphorylase / Q000032:analysis*; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor; D049452:Green Fluorescent Proteins; D019394:Ki-67 Antigen; D008164:Luminescent Proteins; D009687:Nuclear Proteins; D013939:Thymidine Phosphorylase; C067980:CD68 antigen, human; D000097382:CD68 Molecule