| First Author | Horiguchi H | Year | 2021 |
| Journal | Oncogene | Volume | 40 |
| Issue | 1 | Pages | 55-67 |
| PubMed ID | 33051596 | Mgi Jnum | J:301426 |
| Mgi Id | MGI:6505911 | Doi | 10.1038/s41388-020-01505-7 |
| Citation | Horiguchi H, et al. (2021) Stroma-derived ANGPTL2 establishes an anti-tumor microenvironment during intestinal tumorigenesis. Oncogene 40(1):55-67 |
| abstractText | Previous studies show that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) functions as a tumor promoter in some cancer contexts. However, we recently reported that host ANGPTL2 also shows tumor suppressive activity by enhancing dendritic cell-mediated CD8(+) T cell anti-tumor immune responses in mouse kidney cancer and murine syngeneic models. However, mechanisms underlying ANGPTL2-mediated tumor suppression are complex and not well known. Here, we investigated ANGPTL2 tumor suppressive function in chemically-induced intestinal tumorigenesis. ANGPTL2 deficiency enhanced intestinal tumor growth in an experimental mouse colitis-associated colon cancer (CAC) model. Angptl2-deficient mice also showed a decrease not only in CD8(+) T cell responses but in CD4(+) T cell responses during intestinal tumorigenesis. Furthermore, we show that stroma-derived ANGPTL2 can activate the myeloid immune response. Notably, ANGPTL2 drove generation of immunostimulatory macrophages via the NF-kappaB pathway, accelerating CD4(+) T helper 1 (Th1) cell activation. These findings overall provide novel insight into the complex mechanisms underlying ANGPTL2 anti-tumor function in cancer pathology. |
