Serum Amyloid A Promotes Inflammation-Associated Damage and Tumorigenesis in a Mouse Model of Colitis-Associated Cancer

Tanja A. Davis, Daleen Conradie, Preetha Shridas, Frederick C. de Beer, Anna Mart Engelbrecht, Willem J.S. de Villiers

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background & Aims: 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. Although it previously has been suggested as a suitable biomarker for monitoring disease activity in patients diagnosed with Crohn's disease, the role of the acute-phase protein serum amyloid A (SAA) in inflammatory bowel disease remains unclear. In this 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 (Saa1/2-/-) mice by following the azoxymethane/dextran sulfate sodium protocol. Disease activity was monitored throughout the study while colon and tumor tissues were harvested for subsequent use in cytokine analyses, Western blot, and immunohistochemistry +experiments. Results: We observed attenuated disease activity in mice deficient for Saa1/2 as evidenced by decreased weight loss, increased stool consistency, decreased rectal bleeding, and decreased colitis-associated tissue damage. Macrophage infiltration, including CD206+ M2-like macrophages, also was attenuated in SAA knockout mice, while levels of interleukin 4, interleukin 10, and tumor necrosis factor-ɑ were decreased in the distal colon. Mice deficient for SAA also showed a decreased tumor burden, and tumors were found to have increased apoptotic activity coupled with decreased expression for markers of proliferation. Conclusion: Based on these findings, we conclude that SAA has an active role in inflammatory bowel disease and that it could serve as a therapeutic target aimed at decreasing chronic inflammation and the associated risk of developing colitis-associated cancer.

Original languageEnglish
Pages (from-to)1329-1341
Number of pages13
JournalCMGH
Volume12
Issue number4
DOIs
StatePublished - Jan 2021

Bibliographical note

Funding Information:
Funding This work was supported financially by the South African Medical Research Council (A.-M.E.), the Cancer Association of South Africa (A.-M.E.), and National Research Foundation of South Africa grants 112018 (T.A.D.) and 118566 (A.-M.E.). The funding bodies had no role in the study design, collection, analyses, or interpretation of the data.

Publisher Copyright:
© 2021 The Authors

Keywords

  • Colitis-Associated Cancer
  • Colon Cancer
  • Inflammation
  • Macrophage
  • Serum Amyloid A

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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