Abstract
Background: Previous research has shown that the Serum Amyloid A (SAA) protein family is intricately involved in inflammatory signaling and various disease pathologies. We have previously demonstrated that SAA is associated with increased colitis disease severity and the promotion of tumorigenesis. However, the specific role of SAA proteins in breast cancer pathology remains unclear. Therefore, we investigated the role of systemic SAA1 and SAA2 (SAA1/2) in a triple-negative breast cancer mouse model.
Methods: Syngeneic breast tumors were established in wild-type mice, and mice lacking the SAA1/2 (SAADKO). Subsequently, tumor volume was monitored, species survival determined, the inflammatory profiles of mice assessed with a multiplex assay, and tumor molecular biology and histology characterized with Western blotting and H&E histological staining.
Results: WT tumor-bearing mice had increased levels of plasma SAA compared to wild-type control mice, while SAADKO control and tumor-bearing mice presented with lower levels of SAA in their plasma. SAADKO tumor-bearing mice also displayed significantly lower concentrations of systemic inflammatory markers. Tumors from SAADKO mice overall had lower levels of SAA compared to tumors from wild-type mice, decreased apoptosis and inflammasome signaling, and little to no tumor necrosis.
Conclusions: We demonstrated that systemic SAA1/2 stimulates the activation of the NLRP3 inflammasome in breast tumors, leading to the production of pro-inflammatory cytokines. This, in turn, promoted apoptosis and tumor necrosis but did not significantly impact tumor growth or histological grading.
Document Type
Article
Publication Date
2024
Digital Object Identifier (DOI)
https://doi.org/10.3390/biology13090654
Funding Information
This work was supported by the National Research Foundation (NRF) [grant number 118566], the South African Medical Research Council (SAMRC) [grant number CP 5081], and the Cancer Association of South Africa (CANSA) [grant number CP 41966]. Funding sources had no involvement in the study design, the collection, analysis, and interpretation of data, the writing of the report, or the decision to submit the article for publication.
Repository Citation
Olivier, Daniel Wilhelm; Eksteen, Carla; du Plessis, Manisha; de Jager, Louis; Engelbrecht, Lize; McGregor, Nathaniel Wade; Shridas, Preetha; de Beer, Frederick C.; de Villiers, Willem J. S.; Pretorius, Etheresia; and Engelbrecht, Anna-Mart, "Inflammation and Tumor Progression: The Differential Impact of SAA in Breast Cancer Models" (2024). Saha Cardiovascular Research Center Faculty Publications. 86.
https://uknowledge.uky.edu/cvrc_facpub/86
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Notes/Citation Information
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).