TFPI2在肿瘤转移中的作用：一把具有临床意义的双刃剑

摘要(中文译文)

组织因子途径抑制物2（TFPI2）是一种丝氨酸蛋白酶抑制物，在肿瘤转移中发挥多方面作用。传统上认为它是一种转移抑制因子，可抑制细胞外基质（ECM）重塑、上皮-间质转化及血管生成。然而，新近证据表明，TFPI2在胶质母细胞瘤、黑色素瘤及其他癌症中通过促进免疫抑制性肿瘤微环境、介导病理性ECM重塑以及增强血管生成和血行播散来促进肿瘤进展。值得注意的是，即使在同一个转移级联过程中，TFPI2也表现出不同的表达模式以及依赖于情境的相反功能，既可充当转移抑制因子，也可充当转移促进因子。本综述总结其依赖于情境的调控机制，从结构双重性、微环境异质性及受体差异方面探讨其 underlying 基础，并评估其作为治疗靶点的潜力。未来研究应阐明时空微环境动态，以支持早期筛查和精准干预。

Abstract

Tissue factor pathway inhibitor 2 (TFPI2), a serine protease inhibitor, plays a multifaceted role in tumor metastasis. Traditionally viewed as a metastasis suppressor, it inhibits extracellular matrix (ECM) remodeling, epithelial-mesenchymal transition, and angiogenesis. However, emerging evidence indicates that TFPI2 promotes tumor progression in glioblastoma, melanoma, and other cancers by fostering an immunosuppressive tumor microenvironment, mediating pathological ECM remodeling, and enhancing angiogenesis and hematogenous dissemination. Notably, even within the same metastatic cascade, TFPI2 exhibits divergent expression patterns and context-dependent opposing functions, acting either as a metastasis suppressor or promoter. This review summarizes its context-dependent regulatory mechanisms, investigates the underlying basis from structural duality, microenvironmental heterogeneity, and receptor differences, and evaluates its potential as a therapeutic target. Future research should elucidate spatiotemporal microenvironmental dynamics to support early screening and precise intervention.

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