The Two Faces of Angiopoietin-Like Protein 2 in Cancer

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.