Abstract PO4-25-05: LYVE-1 expressing macrophages modulate the extracellular matrix and contribute to mammary tumor growth

Abstract Macrophages represent a heterogeneous myeloid population with varied functions in normal tissue and tumors. We identify a tissue resident macrophage subpopulation marked by the protein LYVE-1 in both the female mammary gland and mammary tumor. In a genetic LYVE-1+ macrophage deletion model, loss of LYVE-1+ macrophage leads to accumulation of the extracellular matrix glycosaminoglycan hyaluronan. Further, qRT-PCR of tissue lacking LYVE-1+ macrophages yields a gene signature associated with extracellular matrix disorganization. Supporting a tissue remodeling functionality, inducing a LYVE-1 macrophages phenotype in vitro prompts HA internalization and increases hyaluronidase expression. In a murine tumor model, deletion of LYVE-1+ macrophages slows tumor progression and increases HA accumulation, suggesting an anti-tumorigenic, tissue remodeling phenotype. LYVE-1+ macrophages preferentially localize to HA dense regions of tumors, specifically in the tumor stroma, while scRNA-seq of murine tumors demonstrates a LYVE-1+ macrophage phenotype associated with tissue remodeling and immunosuppression. Our data illustrate a LYVE-1+ macrophage population critical for HA homeostasis and tumor progression. Citation Format: Alexis Elfstrum, Annisa Rumahorbo, Braedan McCluskey, Emma Nelson, Kaylee Schwertfeger. LYVE-1 expressing macrophages modulate the extracellular matrix and contribute to mammary tumor growth abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-25-05.