TFPI-2对恶性肿瘤细胞增殖凋亡 侵袭转移调控作用的研究进展  

Research progress on effects of TFPI-2 on proliferation,apoptosis,and metastasis of malignant tumors cells

作　　者：魏熙胤[1] 臧凤琳[2] 孙保存[2] 

机构地区：[1]天津医科大学肿瘤医院肿瘤研究所公共实验室,国家肿瘤临床医学研究中心,天津市肿瘤防治重点实验室,天津市300060 [2]天津医科大学肿瘤医院病理科,天津市300060

出　　处：《中国肿瘤临床》2014年第21期1399-1402,共4页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金青年科学基金项目(编号81001020);天津市卫生局科技基金项目(编号2010KZ70)资助~~

摘　　要：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Cp G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。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.

关 键 词：TFPI-2 恶性肿瘤 凋亡 转移 血管生成 

分 类 号：R730.2[医药卫生—肿瘤]