Evidence map›Paper›PMID 38717149›Full record

ArticleCancer research communications2024

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

Alexis K Elfstrum, Annisa H Rumahorbo, Lyndsay E Reese, Emma V Nelson, Braedan M McCluskey, Kathryn L Schwertfeger

Abstract read
In one paragraph

Article in Cancer research communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Alexis K ElfstrumMicrobiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota, Minneapolis, Minnesota.ORCID 0000-0003-2908-3527
Annisa H RumahorboDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota.ORCID 0009-0005-1096-3753
Lyndsay E ReeseDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota.ORCID 0009-0003-1560-4886
Emma V NelsonDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota.ORCID 0009-0001-0450-2572
Braedan M McCluskeyUniversity of Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota.ORCID 0000-0001-6423-7048
Kathryn L SchwertfegerDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota.ORCID 0000-0002-9755-7774

Funding

University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UL1TR002494 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R, WEISDORF, DANIEL J · 2018 to 2022
$34.9M
IMMUNOLOGY TRAINING PROGRAMT32AI007313 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Carla Rothlin · 1989 to 2026
$5.7M
Contributions of FGFR-Mediated Tumor-Stromal Interactions to Breast Cancer Growth and ProgressionR01CA215052 · NCI · UNIVERSITY OF MINNESOTA · PI Kathryn L Schwertfeger · 2017 to 2026
$3.6M
Functions of ductal- and stromal-associated macrophages in the mammary glandR01HD106929 · NICHD · TULANE UNIVERSITY OF LOUISIANA · PI Heather L Machado, Kathryn L Schwertfeger · 2022 to 2026
$2.4M
Defining the contributions of Lyve-1 expressing macrophages to breast cancer growth and progressionR01CA265004 · NCI · UNIVERSITY OF MINNESOTA · PI Kathryn L Schwertfeger · 2022 to 2026
$2.0M
Regulation of tissue resident macrophages during mammary gland developmentR01HD095858 · NICHD · UNIVERSITY OF MINNESOTA · PI SCHWERTFEGER, KATHRYN L · 2018 to 2022
$1.9M
HHS | National Institutes of Health (NIH) R01CA215052HHS | National Institutes of Health (NIH) R01CA265004HHS | National Institutes of Health (NIH) R01HD106929HHS | National Institutes of Health (NIH) R01HD95858HHS | National Institutes of Health (NIH) T32AI007313NCATS NIH HHS UL1 TR002494NCI NIH HHS R01 CA215052NCI NIH HHS R01 CA265004NIAID NIH HHS T32 AI007313NICHD NIH HHS R01 HD095858NICHD NIH HHS R01 HD106929
6 · The paper itself

Abstract

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.

Indexed as

Extracellular MatrixHyaluronic AcidMacrophagesMammary Neoplasms, ExperimentalTumor MicroenvironmentAnimalsBreast NeoplasmsFemaleMammary Glands, AnimalMembrane Transport ProteinsMiceStromal CellsVesicular Transport ProteinsHyaluronic AcidLYVE1 protein, mouseMembrane Transport ProteinsVesicular Transport Proteins

Identifiers

PMID38717149
PMCPMC11141485

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.