P075 Calponin 2 protects against colitis associated cancer in mice through mediating inflammatory responses
Xu B., Jiang M., Qiu Z., Li X., Chen D., Chu Y., Wang W., Liang J., Wu K.
The Fourth Military Medical University, State Key Laboratory of Cancer Biology & Institute of Digestive Diseases, Xi'an, Shaanxi, China
Calponin 2 is involved in many types of malignancies, and it has been recognized as a regulator of macrophage motility and phagocytosis. We investigated whether Calponin 2 could represents a functional link between the inflammation and cancer.
Calponin 2−/− mice and C57BL/6 wild type littermate controls were intraperitoneally injected with azoxymethane (AOM) followed by three cycles of 2.5% dextran sulfate sodium (DSS) in drinking water to induce colitis associated cancer (CAC). Acute colitis and chronic colitis were triggered by DSS. Mesenchymal stem cells (MSCs) were collected from WT and Calponin 2v mice and bone marrow reconstitution was performed. Macrophages were eliminated and the severity of colitis were evaluated. Intestinal crypts were isolated and incubated within or without macrophages for 24 hours.
Calponin 2−/− mice developed significant tumorigenesis, increased COX-2 and IL-6 production, and showed signs of increased phosphorylation of NF-κB and STAT3 in colitis and CAC. This effects were associated with increased Calponin free macrophage infiltration, and the reduction in colitis caused by macrophage elimination were observed in Calponin 2−/− mice. Moreover, increased cell proliferation was observed in organoids when co-cultured with Calponin 2−/− macrophages.
Lack of Calponin 2 can promote progression of CAC by mediating macrophages infiltration, leading to increased IL-6 secretion, thus triggers NF-κB and STAT3 phosphorylation and development of CAC. Treatment with Calponin 2 mimic seems to be a highly intriguing therapeutic concept for inflammation-associated tumor development.