Horiguchi Haruki, Kadomatsu Tsuyoshi, Oike Yuichi
Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Department of Aging and Geriatric Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Cancer Sci. 2025 Mar;116(3):592-599. doi: 10.1111/cas.16434. Epub 2024 Dec 17.
The tumor microenvironment is composed of tumor cells and various stromal cell types, such as immune cells, fibroblasts, and vascular cells. Signaling interactions between tumor and stromal cells orchestrate the tumor microenvironment's contribution to tumor progression. Angiopoietin-like protein 2 (ANGPTL2) is a secreted glycoprotein homologous to angiopoietins. Previous studies indicate that tumor cell-derived ANGPTL2 serves as a tumor promoter. However, recent studies suggest that tumor stroma-derived ANGPTL2 shows tumor-suppressive activity by enhancing anti-tumor immune responses, supporting a dual function for ANGPTL2 in cancer pathology. Such complexity can complicate development of effective therapeutic strategies targeting ANGPTL2. In this Review, we focus on ANGPTL2 activity in the tumor microenvironment and its function in anti-cancer immunity.
肿瘤微环境由肿瘤细胞和各种基质细胞类型组成，如免疫细胞、成纤维细胞和血管细胞。肿瘤细胞与基质细胞之间的信号相互作用协调了肿瘤微环境对肿瘤进展的作用。血管生成素样蛋白2（ANGPTL2）是一种与血管生成素同源的分泌型糖蛋白。先前的研究表明，肿瘤细胞衍生的ANGPTL2起到肿瘤促进剂的作用。然而，最近的研究表明，肿瘤基质衍生的ANGPTL2通过增强抗肿瘤免疫反应显示出肿瘤抑制活性，这支持了ANGPTL2在癌症病理学中的双重功能。这种复杂性可能会使针对ANGPTL2的有效治疗策略的开发变得复杂。在本综述中，我们重点关注ANGPTL2在肿瘤微环境中的活性及其在抗癌免疫中的功能。
