CAJ | 학술논문

组织因子途径抑制物-2（tissue factor pathway inhibitor-2，TFPI-2）是具有库尼（Kunitz）结构域的丝氨酸蛋白酶抑制剂。新近发现，TFPI-2在恶性肿瘤中表达降低，并与肿瘤转移、侵袭等恶性生物学行为密切相关。该分子表达的分子调控机制包括启动子CpG岛超甲基化、ERK1/2信号途径、JNK信号途径等。TFPI-2的主要功能体现在维持肿瘤微环境的稳定性，抑制肿瘤细胞的生长、侵袭和转移。目前认为，TFPI-2在调节细胞增殖、凋亡以及血管生成拟态方面也发挥重要作用。本文就TFPI-2在肿瘤中的表达及调控机制、细胞凋亡、血管生成中作用进行综述，为其在肿瘤的预防、诊断及基因治疗中开展深入研究提供理论基础。
조직인자도경억제물-2（tissue factor pathway inhibitor-2，TFPI-2）시구유고니（Kunitz）결구역적사안산단백매억제제。신근발현，TFPI-2재악성종류중표체강저，병여종류전이、침습등악성생물학행위밀절상관。해분자표체적분자조공궤제포괄계동자CpG도초갑기화、ERK1/2신호도경、JNK신호도경등。TFPI-2적주요공능체현재유지종류미배경적은정성，억제종류세포적생장、침습화전이。목전인위，TFPI-2재조절세포증식、조망이급혈관생성의태방면야발휘중요작용。본문취TFPI-2재종류중적표체급조공궤제、세포조망、혈관생성중작용진행종술，위기재종류적예방、진단급기인치료중개전심입연구제공이론기출。
Tissue factor pathway inhibitor-2 (TFPI-2), a member of the Kunitz-type family, is a broad-spectrum serine proteinase inhibitor. The expression of TFPI-2 is inversely related to increasing degree of malignancy, suggesting a role of TFPI-2 in the mainte-nance of tumor stability and inhibition of the growth of neoplasma. Aberrant methylation of TFPI-2 promoter cytosine-phosphorothio-ate-guanine (CpG) islands has been widely documented to be responsible for diminished expression of TFPI-2 mRNA and protein dur-ing cancer progression. TFPI-2 expression is significantly up-regulated by the ERK1/2 and JNK signaling pathways and modestly in-creased by VEGF, TNF-alpha, and fibroblast growth factor in time-and dose-dependent manners. TFPI-2 can maintain the stability of the tumor environment and inhibit invasiveness and growth of neoplasms. TFPI-2 has also been shown to regulate proliferation, apopto-sis, and vasculogenic mimicry of tumor cells, which may contribute significantly to tumor growth inhibition. Restoration of TFPI-2 ex-pression in tumor tissue inhibits tumor growth and metastasis, which creates a novel possibility of cancer patient treatment. This review focuses on the expression and the molecular regulation mechanisms of TFPI-2 in malignant tumors that control the functions of TFPI-2 in proliferation, apoptosis, and angiogenesis. Insight into these processes will improve our understanding of TFPI-2 and provide new ap-proaches for rational treatment strategies.