Restoration of tissue factor pathway inhibitor inhibits invasion and tumor growth in vitro and in vivo in a malignant meningioma cell line

Shakuntala Kondraganti, Christopher S. Gondi, Meena Gujrati, Ian McCutcheon, Dzung H. Dinh, Jasti S. Rao, William C. Olivero

Research output: Contribution to journalArticle

Abstract

Tissue factor pathway inhibitor 2 (TFPI-2) is a 32-kDa extracellular matrix-associated kunitz-type serine proteinase inhibitor. It is secreted by all vascular cells and plays a role in tumor invasion and metastasis, presumably by plasmin-mediated matrix remodeling. Previous studies have shown high expression of TFPI-2 by benign tumors and low or absent expression in highly malignant tumors. Malignant meningiomas constitute 10-15% of all meningiomas and our previous studies revealed loss of expression of TFPI-2 in malignant gliomas. To investigate the role of TFPI-2 in the invasiveness of malignant meningiomas, we stably transfected the human meningioma cell line, IOMM-Lee, with a vector capable of expressing a transcript complementary to the full length of TFPI-2 mRNA in a sense orientation. Restoration of TFPI-2 led to decreased invasiveness of transfected cells compared to parental and vector controls in Matrigel and spheroid assays and inhibition of angiogenesis in in vitro co-cultures with human umbilical vein endothelial cells (HUVEC) and in vivo dorsal skin assay studies. As assessed by Western blotting, we also observed increased expression of BAX, cytochrome c and caspase 3 as well as decreased expression of XIAP (X-linked inhibitor of apoptosis). Finally, TFPI-2 overexpression inhibited intracranial tumor formation in nude mice. Our data substantiate our previous observation that TFPI-2 plays an important role in tumor progression and has potential in anti-cancer therapy.

Original languageEnglish (US)
Pages (from-to)25-32
Number of pages8
JournalInternational Journal of Oncology
Volume29
Issue number1
StatePublished - Jul 2006

Fingerprint

Meningioma
Cell Line
Growth
Neoplasms
Serine Proteinase Inhibitors
tissue-factor-pathway inhibitor 2
lipoprotein-associated coagulation inhibitor
In Vitro Techniques
Fibrinolysin
Human Umbilical Vein Endothelial Cells
Coculture Techniques
Nude Mice
Glioma
Caspase 3
Extracellular Matrix
Blood Vessels
Western Blotting
Apoptosis
Neoplasm Metastasis
Messenger RNA

Keywords

  • Angiogenesis
  • Invasion
  • TFPI-2

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kondraganti, S., Gondi, C. S., Gujrati, M., McCutcheon, I., Dinh, D. H., Rao, J. S., & Olivero, W. C. (2006). Restoration of tissue factor pathway inhibitor inhibits invasion and tumor growth in vitro and in vivo in a malignant meningioma cell line. International Journal of Oncology, 29(1), 25-32.

Restoration of tissue factor pathway inhibitor inhibits invasion and tumor growth in vitro and in vivo in a malignant meningioma cell line. / Kondraganti, Shakuntala; Gondi, Christopher S.; Gujrati, Meena; McCutcheon, Ian; Dinh, Dzung H.; Rao, Jasti S.; Olivero, William C.

In: International Journal of Oncology, Vol. 29, No. 1, 07.2006, p. 25-32.

Research output: Contribution to journalArticle

Kondraganti, S, Gondi, CS, Gujrati, M, McCutcheon, I, Dinh, DH, Rao, JS & Olivero, WC 2006, 'Restoration of tissue factor pathway inhibitor inhibits invasion and tumor growth in vitro and in vivo in a malignant meningioma cell line', International Journal of Oncology, vol. 29, no. 1, pp. 25-32.
Kondraganti, Shakuntala ; Gondi, Christopher S. ; Gujrati, Meena ; McCutcheon, Ian ; Dinh, Dzung H. ; Rao, Jasti S. ; Olivero, William C. / Restoration of tissue factor pathway inhibitor inhibits invasion and tumor growth in vitro and in vivo in a malignant meningioma cell line. In: International Journal of Oncology. 2006 ; Vol. 29, No. 1. pp. 25-32.
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