Role of the Tumor-Immune Interplay in Breast Cancer Metastasis
Abstract
Dissemination of breast cancer (BCa) to distant organs is the main cause of patient death and treatment failure, thereby representing the major barrier for cure of BCa. Scavenger receptor A (SRA/CD204) is an innate pattern recognition receptor primarily expressed on the host cells of myeloid origin (e.g., macrophage) and displays pleiotropic functions in immune homeostasis. Using a genetic BCa model (i.e., MMTV-PyMT), we have shown that lack of SRA suppresses spontaneous mammary tumorigenesis and that the partial loss of SRA considerably reduces BCa metastasis in lungs and lymph nodes. We further established a critical role of SRA for promoting BCa metastasis using an orthotopic BCa implantation model. The SRA-enhanced BCa metastasis appears to involve functional modulation of macrophages in the metastatic niche, indicated by polarization of alveolar macrophages toward a M1-like phenotype in the absence of SRA. Additionally, the loss of SRA conferred macrophages increased cytolytic capacity during interactions with BCa cells, supporting that SRA function acts as an important determinant of macrophage-mediated innate immune surveillance of BCa metastasis. Given the critical role of SRA in BCa tumorigenesis and metastasis, these findings may offer new opportunities to develop novel SRA-targeting approaches for treatment of metastatic BCa.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2023
- Accession Number
- AD1205960
Entities
People
- Wang Xiang-yang
Organizations
- Virginia Commonwealth University