The Role of Tissue Factor Pathway Inhibitor-2 in Cancer Biology

Ewa Sierko; Marek Z. Wojtukiewicz; Walter Kisiel

doi:10.1055/s-2007-991532

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2007; 33(7): 653-659
DOI: 10.1055/s-2007-991532

The Role of Tissue Factor Pathway Inhibitor-2 in Cancer Biology

Ewa Sierko¹ ^, ² , Marek Z. Wojtukiewicz¹ ^, ² , Walter Kisiel³

¹Department of Oncology, Medical University, Bialystok, Poland
²Comprehensive Cancer Center, Bialystok, Poland
³Department of Pathology, University of New Mexico Health Sciences Center, University of New Mexico, Albuquerque, New Mexico

Abstract

ABSTRACT

Tissue factor pathway inhibitor-2 (TFPI-2), a member of the Kunitz-type serine proteinase inhibitor family, is a structural homologue of tissue factor pathway inhibitor (TFPI). The expression of TFPI-2 in tumors is inversely related to an increasing degree of malignancy, which may suggest a role for TFPI-2 in the maintenance of tumor stability and inhibition of the growth of neoplasms. TFPI-2 inhibits the tissue factor/factor VIIa (TF/VIIa) complex and a wide variety of serine proteinases including plasmin, plasma kallikrein, factor XIa, trypsin, and chymotrypsin. Aberrant methylation of TFPI-2 promoter cytosine-phosphorothioate-guanine (CpG) islands in human cancers and cancer cell lines was widely documented to be responsible for diminished expression of mRNA encoding TFPI-2 and decreased or inhibited synthesis of TFPI-2 protein during cancer progression. Furthermore, an aberrantly spliced variant of TFPI-2 mRNA (designated asTFPI-2) was detected, which represents an untranslated form of TFPI-2. The levels of asTFPI-2 were very low or undetectable in normal cells but markedly upregulated in neoplastic tissue. TFPI-2 functions in the maintenance of the stability of the tumor environment and inhibits invasiveness and growth of neoplasms, as well as metastases formation. TFPI-2 has also been shown to induce apoptosis and inhibit angiogenesis, which may contribute significantly to tumor growth inhibition. Restoration of TFPI-2 expression in tumor tissue inhibits invasion, tumor growth, and metastasis, which creates a novel possibility of cancer patient treatment. However, more information is still needed to define the precise role of TFPI-2 in human tumor biology.

KEYWORDS

Coagulation inhibitors - TFPI-2 - cancer

Full Text

References

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Dr. Marek Z Wojtukiewicz

Department of Oncology, Medical University

12 Ogrodowa St., 15-027 Bialystok, Poland

Email: m.wojtukiewicz@neostrada.pl