SRA facilitates breast cancer metastasis by regulating tumor-immune interplay 2804

Abstract Description Objectives The emerging evidence indicates that cancer-immune crosstalk can define tumor behaviors in invasion and metastasis. Here we examine the potential impact of pattern recognition scavenger receptor A (SRA), highly expressed on macrophages, for orchestrating breast cancer (BCa) metastasis. Methods Spontaneous or experimental lung metastases were induced in wild-type and SRA knockout mice using luciferase-expressing mouse mammary tumor cells, followed by imaging analysis. The role of macrophages in mediating SRA-promoted BCa metastasis was examined using cell depletion and trans-well invasion assays. The SRA-dependent pro-metastatic activity was confirmed using SRA-blocking antibodies. Results The loss of SRA markedly impaired pulmonary metastasis of BCa, which was abrogated upon depletion of macrophages. SRA-expressing macrophages support an invasive phenotype and metastatic potential of BCa cells by promoting epithelial mesenchymal transition, which was mediated mainly through activation of chemokine signaling in cancer cells. SRA blockade effectively inhibits the invasive phenotype of BCa in vitro and its lung metastasis in vivo. Conclusion Our findings identify SRA on macrophages as a novel regulator of BCa metastasis, which may be exploited to develop SRA-targeted therapies for metastatic BCa. Funding Sources W81XWH-21-1-0056 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)