A novel role of tissue factor pathway inhibitor-2 in apoptosis of malignant human gliomas.

A. Tasiou, S. D. Konduri, N. Yanamandra, D. H. Dinh, W. C. Olivero, M. Gujrati, M. Obeyesekere, J. S. Rao

Research output: Contribution to journalArticle

Abstract

Tissue factor pathway inhibitor-2 (TFPI-2) is a 32 kDa serine protease inhibitor found at high levels in extracellular matrix. Recombinant human TFPI-2 has recently been shown to be a strong inhibitor of trypsin, plasmin, plasma kallikrein, and factor XIa amidolytic activity. Earlier studies in our laboratory showed that the expression of TFPI-2 is lost during tumor progression in human gliomas. We stably transfected this protease inhibitor in multiform glioblastoma cell line (SNB-19) and in low-grade glioma cell line (Hs683) in sense and antisense orientation respectively. This confirmed that the upregulation/down-regulation of TFPI-2 plays a significant role in the invasive behavior of human gliomas both in vitro and in vivo models. Collectively, these results suggested an idea to determine whether TFPI-2 is necessary for cell survival and inhibition of tumor formation in nude mice, due to apoptosis of intracerebrally injected SNB-19 cells. In the present study we determined p-ERK levels and found that they are decreased in TFPI-2 over-expressed clones (SNB-19) and increased in TFPI-2 down-regulated clones (Hs683). We also checked the levels of BAX/BCl-2, caspases (for e.g., 9, 7, 3, 8), PARP, cytochrome-c and Apaf-1. Moreover, the increase of apoptosis in vitro is associated with increased and decreased expression of apoptotic protein BAX in sense clones (SNB-19) and antisense clones (Hs683) respectively, when compared to controls and vice versa with Bcl-2 the anti-apoptotic protein. Caspases (9, 7 and 3), cytochrome-c, Apaf-1 and PARP levels are increased in SNB-19 and decreased in Hs683. Caspase 8 was not expressed in either cell line. Caspases 9 and 3 activity assay revealed higher activity in sense clones (SNB-19) but lesser in antisense clones (Hs683) compared to controls. This is the first report of TFPI-2 playing a novel role in cell survival in human gliomas.

Original languageEnglish (US)
Pages (from-to)591-597
Number of pages7
JournalInternational journal of oncology
Volume19
Issue number3
DOIs
StatePublished - Sep 2001

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Tasiou, A., Konduri, S. D., Yanamandra, N., Dinh, D. H., Olivero, W. C., Gujrati, M., Obeyesekere, M., & Rao, J. S. (2001). A novel role of tissue factor pathway inhibitor-2 in apoptosis of malignant human gliomas. International journal of oncology, 19(3), 591-597. https://doi.org/10.3892/ijo.19.3.591