دورية أكاديمية
أعرض في EDS

LYVE-1-expressing Macrophages Modulate the Hyaluronan-containing Extracellular Matrix in the Mammary Stroma and Contribute to Mammary Tumor Growth.

التفاصيل البيبلوغرافية
العنوان: LYVE-1-expressing Macrophages Modulate the Hyaluronan-containing Extracellular Matrix in the Mammary Stroma and Contribute to Mammary Tumor Growth.
المؤلفون: Elfstrum AK; Microbiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota, Minneapolis, Minnesota., Rumahorbo AH; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota., Reese LE; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota., Nelson EV; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota., McCluskey BM; University of Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota., Schwertfeger KL; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota.; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.; Center for Immunology, University of Minnesota, Minneapolis, Minnesota.
المصدر: Cancer research communications [Cancer Res Commun] 2024 May 31; Vol. 4 (5), pp. 1380-1397.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 9918281580506676 Publication Model: Print Cited Medium: Internet ISSN: 2767-9764 (Electronic) Linking ISSN: 27679764 NLM ISO Abbreviation: Cancer Res Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Philadelphia, Pennsylvania] : American Association for Cancer Research, [2021]-
مواضيع طبية MeSH: Hyaluronic Acid*/metabolism , Macrophages*/metabolism , Macrophages*/immunology , Macrophages*/pathology , Extracellular Matrix*/metabolism , Extracellular Matrix*/pathology , Tumor Microenvironment*, Animals ; Female ; Mice ; Vesicular Transport Proteins/genetics ; Vesicular Transport Proteins/metabolism ; Mammary Neoplasms, Experimental/metabolism ; Mammary Neoplasms, Experimental/pathology ; Mammary Neoplasms, Experimental/immunology ; Mammary Neoplasms, Experimental/genetics ; Stromal Cells/metabolism ; Stromal Cells/pathology ; Humans ; Mammary Glands, Animal/metabolism ; Mammary Glands, Animal/pathology ; Breast Neoplasms/pathology ; Breast Neoplasms/metabolism ; Breast Neoplasms/genetics ; Breast Neoplasms/immunology
مستخلص: Macrophages represent a heterogeneous myeloid population with diverse functions in normal tissues and tumors. While macrophages expressing the cell surface marker lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) have been identified in stromal regions of the normal mammary gland and in the peritumoral stroma, their functions within these regions are not well understood. Using a genetic mouse model of LYVE-1+ macrophage depletion, we demonstrate that loss of LYVE-1+ macrophages is associated with altered extracellular matrix remodeling in the normal mammary gland and reduced mammary tumor growth in vivo. In further studies focused on investigating the functions of LYVE-1+ macrophages in the tumor microenvironment, we demonstrate that LYVE-1 expression correlates with an increased ability of macrophages to bind, internalize, and degrade hyaluronan. Consistent with this, we show that depletion of LYVE-1+ macrophages correlates with increased hyaluronan accumulation in both the normal mammary gland and in mammary tumors. Analysis of single-cell RNA sequencing of macrophages isolated from these tumors reveals that depletion of LYVE-1+ macrophages in tumors drives a shift in the majority of the remaining macrophages toward a proinflammatory phenotype, as well as an increase in CD8+ T-cell infiltration. Together, these findings indicate that LYVE-1+ macrophages represent a tumor-promoting anti-inflammatory subset of macrophages that contributes to hyaluronan remodeling in the tumor microenvironment.
Significance: We have identified a macrophage subset in mouse mammary tumors associated with tumor structural components. When this macrophage subset is absent in tumors, we report a delay in tumor growth and an increase in antitumor immune cells. Understanding the functions of distinct macrophage subsets may allow for improved therapeutic strategies for patients with breast cancer.
(© 2024 The Authors; Published by the American Association for Cancer Research.)
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معلومات مُعتمدة: T32 AI007313 United States AI NIAID NIH HHS; R01HD106929 HHS | National Institutes of Health (NIH); R01 CA265004 United States CA NCI NIH HHS; R01HD95858 HHS | National Institutes of Health (NIH); R01 HD106929 United States HD NICHD NIH HHS; R01 HD095858 United States HD NICHD NIH HHS; R01CA215052 HHS | National Institutes of Health (NIH); R01 CA215052 United States CA NCI NIH HHS; R01CA265004 HHS | National Institutes of Health (NIH); UL1 TR002494 United States TR NCATS NIH HHS; T32AI007313 HHS | National Institutes of Health (NIH)
المشرفين على المادة: 9004-61-9 (Hyaluronic Acid)
0 (Vesicular Transport Proteins)
0 (LYVE1 protein, mouse)
تواريخ الأحداث: Date Created: 20240508 Date Completed: 20240531 Latest Revision: 20240603
رمز التحديث: 20240603
مُعرف محوري في PubMed: PMC11141485
DOI: 10.1158/2767-9764.CRC-24-0205
PMID: 38717149
قاعدة البيانات: MEDLINE
الوصف
تدمد:2767-9764
DOI:10.1158/2767-9764.CRC-24-0205