Stroma-derived ANGPTL2 establishes an anti-tumor microenvironment during intestinal tumorigenesis
| Autor: | Daisuke Torigoe, Haruki Horiguchi, Tsuyoshi Kadomatsu, Kazutoyo Terada, Yuichi Oike, Jun Morinaga, Keishi Miyata, Toshiro Moroishi, Michio Sato |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Myeloid Colorectal cancer T cell Cancer Biology medicine.disease 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Immune system Stroma 030220 oncology & carcinogenesis Genetics medicine Cancer research Cell activation Molecular Biology CD8 |
| Zdroj: | Oncogene. 40:55-67 |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | 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-κB 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. |
| Databáze: | OpenAIRE |
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