The role of tissue factor pathway inhibitor-2 in cancer biology
The role of tissue factor pathway inhibitor-2 in cancer biology
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DOI：
10.1055/s-2007-991532
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发表时间：
2007-10-01
影响因子：
5.7
通讯作者：
Kisiel, Walter
中科院分区：
文献类型：
--
作者：
Sierko, Ewa;Wojtukiewicz, Marek Z.;Kisiel, Walter
组织因子途径抑制剂-2 (TFPI-2) 是 Kunitz 型丝氨酸蛋白酶抑制剂家族的成员，是组织因子途径抑制剂 (TFPI) 的结构同系物。肿瘤中TFPI-2的表达与恶性程度的增加呈负相关，这可能表明TFPI-2在维持肿瘤稳定性和抑制肿瘤生长中发挥作用。 TFPI-2 抑制组织因子/因子 VIIa (TF/VIIa) 复合物和多种丝氨酸蛋白酶，包括纤溶酶、血浆激肽释放酶、因子 XIa、胰蛋白酶和糜蛋白酶。人类癌症和癌细胞系中 TFPI-2 启动子胞嘧啶-硫代磷酸-鸟嘌呤 (CpG) 岛的异常甲基化被广泛记录为导致癌症进展期间编码 TFPI-2 mRNA 表达减少以及减少或抑制 TFPI-2 蛋白合成的原因。此外，检测到 TFPI-2 mRNA 的异常剪接变体（称为 TFPI-2），它代表 TFPI-2 的非翻译形式。 asTFPI-2 的水平在正常细胞中非常低或检测不到，但在肿瘤组织中显着上调。 TFPI-2的作用是维持肿瘤环境的稳定性，抑制肿瘤的侵袭和生长以及转移形成。 TFPI-2 还被证明可以诱导细胞凋亡并抑制血管生成，这可能对肿瘤生长抑制有显着贡献。肿瘤组织中TFPI-2表达的恢复可抑制侵袭、肿瘤生长和转移，这为癌症患者的治疗创造了新的可能性。然而，仍需要更多信息来确定 TFPI-2 在人类肿瘤生物学中的精确作用。
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.