Tissue factor expression and angiogenesis in human glioma

Background: Tissue factor (TF), a cell surface receptor of factor VII/VIIa, was initially recognized as an initiator of the extrinsic coagulation pathway. TF has recently been found to be expressed highly in certain types of malignant tumors. In addition, TF expression appears to be a marker for malignant angiogenesis in human solid tumors. However TF expression and its relationship to angiogenesis and tumor progression in human glioma are still unclear. Methods: Quantitative reverse transcription PCR and immunofluorescence were performed on the U251 glioma cell line, 5 normal brain specimens, and 34 glioma surgical specimens. Of the gliomas, 10 were grade IV, 12 grade III, 7 grade II, and 5 grade I. Microvessels were highlighted using a monoclonal antibody specific to human von Willebrand factor. Results: TF was strongly positive in 90% of the grade IV cases, 58% of grade III, 43% of grade II, and 20% of grade I. TF staining was not present in any normal brain specimens. The mean level of TF mRNA in normal brain tissue was 5.0 × 103 copies/μg RNA. Among the gliomas, TF mRNA ranged from 1.7 × 105 to 6.8 × 107 copies/μg, with a mean of 4.6 × 106. TF expression was highest in glioblastomas that showed greatest vascularity. Conclusions: These findings support a role for TF in angiogenesis in glioma. TF is expressed in glioma and the level of expression correlates with the histologic grade of malignancy and vascularity.