Sa1108 SERUM AMYLOID A PROMOTES INFLAMMATION-ASSOCIATED DAMAGE, MACROPHAGE INFILTRATION AND TUMORIGENESIS IN A MOUSE MODEL OF COLITIS-ASSOCIATED COLON CANCER

Background: Identifying new approaches to lessen inflammation, as well as the associated malignant consequences, remains crucial to improving the lives and prognosis of patients diagnosed with inflammatory bowel diseases (IBD).The acute-phase protein Serum Amyloid A (SAA) is implicated in various inflammation-associated pathologies and while it has been suggested as a suitable marker for monitoring disease activity in patients with Crohn's disease, its role in IBD is poorly understood.Furthermore, increased serum SAA levels have been reported for several different types of cancers, including colon cancer.However, whether the increased serum levels are an indirect consequence of the chronic inflammation associated with cancer, or whether SAA has a direct influence on tumorigenesis, is unclear.Aim: In the current study, we aimed to assess the role of SAA in colitis-associated cancer.Methods: We established a model of colitis-associated cancer in wild-type and SAA double knockout (SAADKO, knockout for Saa1 and Saa2) mice using the azoxymethane/dextran sulfate sodium protocol.Disease activity was monitored throughout the study while blood and colon tissue were harvested at euthanasia for subsequent use in cytokine analyses, western blot and immunohistochemistry experiments.Results: Decreased disease activity was observed in SAADKO mice when compared to their wild-type counterparts as indicated by decreased weight loss, increased stool consistency and decreased rectal bleeding.H&E staining of the distal colon revealed that SAADKO mice also displayed less colitis-associated tissue damage.Decreased macrophage infiltration, as identified through immunohistochemical staining with the F4/80 macrophage marker, was observed within the distal colon of SAADKO mice when compared to wild-type mice.In addition, SAADKO mice also displayed decreased Ki-67 staining in areas of dysplasia.Furthermore, a decreased tumor burden was observed in SAADKO mice and tumors were found to exhibit decreased expression of the proliferation marker MCM2, increased expression of the apoptosis marker cleaved Caspase 3, as well as decreased expression of active b-catenin, when compared to tumors isolated from wild-type mice.Conclusion: Based on these findings, we conclude that SAA has an active role in mediating colitis-associated symptoms and promotes tumorigenesis in colitis-associated cancer.Furthermore, we propose that SAA's role extends to the infiltration of macrophages, which holds additional implications for tissue inflammation and possibly inflammationassisted tumor growth.Identifying methods to target and decrease or eliminate SAA levels could improve the quality of life and prognostic outcome of patients diagnosed with IBD. Sa1109