STAT5 is activated in macrophages by breast cancer cell-derived factors and regulates macrophage function in the tumor microenvironment.

Background: In breast cancer, complex interactions between tumor cells and cells within the surrounding stroma, such as macrophages, are critical for tumor growth, progression, and therapeutic response. Recent studies have highlighted the complex nature and heterogeneous populations of macrophages associated with both tumor-promoting and tumor-inhibiting phenotypes. Defining the pathways that drive macrophage function is important for understanding their complex phenotypes within the tumor microenvironment.

Characterizing Macrophage Diversity in Metastasis-Bearing Lungs Reveals a Lipid-Associated Macrophage Subset.

While macrophages are among the most abundant immune cell type found within primary and metastatic mammary tumors, how their complexity and heterogeneity change with metastatic progression remains unknown. Here, macrophages were isolated from the lungs of mice bearing orthotopic mammary tumors for single-cell RNA sequencing (scRNA-seq). Seven distinct macrophage clusters were identified, including populations exhibiting enhanced differential expression of genes related to antigen presentation (), cell cycle (), and interferon signaling ().

Erratum: Witschen, P.M., et al. Tumor Cell Associated Hyaluronan-CD44 Signaling Promotes Pro-Tumor Inflammation in Breast Cancer. 2020, , 1325.

The authors wish to make the following corrections to this paper [...

Tissue-resident macrophages promote extracellular matrix homeostasis in the mammary gland stroma of nulliparous mice.

Tissue-resident macrophages in the mammary gland are found in close association with epithelial structures and within the adipose stroma, and are important for mammary gland development and tissue homeostasis. Macrophages have been linked to ductal development in the virgin mammary gland, but less is known regarding the effects of macrophages on the adipose stroma. Using transcriptional profiling and single-cell RNA sequencing approaches, we identify a distinct resident stromal macrophage subpopulation within the mouse nulliparous mammary gland that is characterized by the expression of Lyve-1, a receptor for the extracellular matrix (ECM) component hyaluronan.

Tumor Cell Associated Hyaluronan-CD44 Signaling Promotes Pro-Tumor Inflammation in Breast Cancer.

Cancer has been conceptualized as a chronic wound with a predominance of tumor promoting inflammation. Given the accumulating evidence that the microenvironment supports tumor growth, we investigated hyaluronan (HA)-CD44 interactions within breast cancer cells, to determine whether this axis directly impacts the formation of an inflammatory microenvironment. Our results demonstrate that breast cancer cells synthesize and fragment HA and express CD44 on the cell surface.