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Macrophages express pattern-recognition receptors, including Class A scavenger receptors (SR-A), which are pivotal in regulating macrophage activation and polarization into distinct phenotypes. SR-A expression is generally correlated with altered cytokine expression indicative of a tumor-supportive M2 macrophage phenotype. While evidence links an increased prevalence of SR-A-expressing TAMs to worse patient outcomes in breast cancer, a definitive role for SR-A and its potential ligands in cancer remains to be fully established. We previously reported that the fibroblast-activated proteinase (FAP)-cleaved collagen is a ligand for SR-A. This study was conducted to assess the role of FAP and SR-A expression in breast cancer. Using mouse models of spontaneous breast cancer, we found that the absence of SR-A, but not FAP, expression significantly delayed the development of palpable tumors and decreased the number of lung metastases in tumor-bearing mice. A soluble SR-A protein was used to demonstrate that SR-A binds to glycans on the surface of breast cancer cells. We used single-cell RNA sequencing and flow cytometry of isolated TAMs and identified a distinct SR-A-dependent TAM subpopulation characterized by high arginase 1 gene expression. Pathway analysis of TAMs associates SR-A expression with activation of transcriptional programs linked to immune-suppressive macrophage phenotypes. These results define a contributory role for SR-A in breast cancer progression and provide new insights into the complex interactions between TAMs and cancer cells in the tumor microenvironment.<\/jats:p>","DOI":"10.1093\/jleuko\/qiag026","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T12:46:08Z","timestamp":1772023568000},"source":"Crossref","is-referenced-by-count":0,"title":["Class A scavenger receptors promote tumor progression and induce a unique macrophage phenotype in a mouse model of spontaneous breast cancer"],"prefix":"10.1093","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2019-4258","authenticated-orcid":false,"given":"Behjatolah","family":"Monzavi-Karbassi","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Arkansas for Medical Sciences , Little Rock, AR 72205 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