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  • Expression of Tissue Factor and Alternatively Spliced Human Tissue Factor in Gliomas

    Final Number:

    Tom C. Zhou; Jennifer E. Hobbs PhD; James P. Chandler MD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2011 Annual Meeting

    Introduction: It has long been recognized that cancers, including gliomas and related brain tumors, are associated with thromboembolic diseases and activators of the coagulation cascade. Accumulating evidence has shown that tissue factor (TF), a trans-membrane activator of the blood coagulation pathway, is involved in the regulation of angiogenesis, cell migration, tumor growth, and inflammation. A soluble form of TF, alternatively spliced human tissue factor (asHTF), is believed to promote cell proliferation and tumor growth. We believe that asHTF and TF may function as a suitable diagnostic marker for solid tumors. Our research will examine the mRNA expression level of TF and asHTF in human gliomas and its correlation to histological grade.

    Methods: Primary cell lines were established from glial tumors of consenting patients. The samples include WHO Grade II astrocytoma or oligodendroglioma, Grade III astrocytoma or oligodendroglioma, and glioblastoma multiforme (GBM). TF and asHTF RNA levels were analyzed by quantitative PCR and correlated with tumor grade.

    Results: Our results demonstrate RNA expression levels of TF and asHTF in primary glioma cell lines. Grade II samples expressed modest levels of TF and asHTF RNA. The majority of GBM samples expressed TF and asHTF, with several samples having high levels of RNA expression. Interestingly, most Grade III samples either lacked TF and asHTF expression or had very low levels of RNA expression.

    Conclusions: Due to the association of TF and asHTF to cancer progression and angiogenesis, it may be of benefit to evaluate the expression level in glioma samples. Here, we noted varying RNA expression levels, which may indicate their intimate role in tumor development. With further analyses in TF and asHTF protein quantification and localization as well as protein chemistry in solid tumors, our study may ultimately lead to the inclusion of TF and asHTF in decisions related to glioma therapies.

    Patient Care: The results from these studies will lead to the development of more accurate diagnostic cues and serve as a decision-making tool to glioma therapies.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) Determine the mRNA expression levels of TF and asHTF in gliomas, 2) Correlate the mRNA expression levels of TF and asHTF with the histological grade of the tumor, and 3) Assess the potential of TF and asHTF as suitable diagnostic markers for gliomas.


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