LYVE-1-expressing macrophages modulate the extracellular matrix in the mammary gland and contribute to mammary tumor growth
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ABSTRACT:
PROVIDER: PRJNA1008238 | ENA |
REPOSITORIES: ENA
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Project description:Macrophages represent a heterogeneous myeloid population with diverse functions in normal tissues and tumors. While LYVE-1 macrophages have been identified in stromal regions of the normal mammary gland and mammary tumor, their functions in these regions remain unknown. Using a genetic LYVE-1+ macrophage deletion model, we demonstrate that loss of LYVE-1+ macrophages leads to accumulation of the extracellular matrix glycosaminoglycan hyaluronan. Consistent with this finding, we demonstrate that LYVE-1 expression correlates with an increased ability of macrophages to bind, internalize, and degrade hyaluronan. Furthermore, we demonstrate that deletion of LYVE-1+ macrophages results in increased hyaluronan accumulation in mammary tumors, which correlates with reduced tumor growth. Finally, using scRNA-seq, we demonstrate that deletion of LYVE-1 macrophages in tumors results in a shift in the remaining macrophages towards a pro-inflammatory phenotype. Together, these findings demonstrate that LYVE-1+ macrophages represent an anti-inflammatory macrophage population that contributes to tissue remodeling in the tumor microenvironment.
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Project description:Identify gene expression changes in the absence of Plk2 Disruptions in polarity and mitotic spindle orientation contribute to the progression and evolution of tumorigenesis. However, little is known about the molecular mechanisms regulating these processes in vivo. Here we demonstrate that Polo-like kinase 2 (Plk2) regulates mitotic spindle orientation in the mammary gland and is a putative tumor suppressor. Plk2 is highly expressed in the mammary gland and is required for proper mammary gland development. Loss of Plk2 leads to increased mammary epithelial cell proliferation and ductal hyperbranching. Additionally a novel role for Plk2 in regulating the orientation of the mitotic spindle and maintaining proper cell polarity in the ductal epithelium was discovered. In support of a tumor suppressor function for Plk2, loss of Plk2 increased the formation of lesions in multiparous glands. Collectively, these results demonstrate a novel role for Plk2 in regulating mammary gland development and as a tumor suppressor in mammary tumorigenesis. Disruptions in polarity and mitotic spindle orientation contribute to the progression and evolution of tumorigenesis. However, little is known about the molecular mechanisms regulating these processes in vivo. Here we demonstrate that Polo-like kinase 2 (Plk2) regulates mitotic spindle orientation in the mammary gland and is a putative tumor suppressor. Plk2 is highly expressed in the mammary gland and is required for proper mammary gland development. Loss of Plk2 leads to increased mammary epithelial cell proliferation and ductal hyperbranching. Additionally a novel role for Plk2 in regulating the orientation of the mitotic spindle and maintaining proper cell polarity in the ductal epithelium was discovered. In support of a tumor suppressor function for Plk2, loss of Plk2 increased the formation of lesions in multiparous glands. Collectively, these results demonstrate a novel role for Plk2 in regulating mammary gland development and as a tumor suppressor in mammary tumorigenesis. Comparison between Plk2 +/+ (n=3) and Plk2 -/- (n=3) mouse mammary epithelial cells
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Project description:Resident macrophages promote homeostasis of hyaluronan-associated extracellular matrix in the mammary gland stroma
| PRJNA623511 | ENA
Project description:Identify gene expression changes in the absence of Plk2 Disruptions in polarity and mitotic spindle orientation contribute to the progression and evolution of tumorigenesis. However, little is known about the molecular mechanisms regulating these processes in vivo. Here we demonstrate that Polo-like kinase 2 (Plk2) regulates mitotic spindle orientation in the mammary gland and is a putative tumor suppressor. Plk2 is highly expressed in the mammary gland and is required for proper mammary gland development. Loss of Plk2 leads to increased mammary epithelial cell proliferation and ductal hyperbranching. Additionally a novel role for Plk2 in regulating the orientation of the mitotic spindle and maintaining proper cell polarity in the ductal epithelium was discovered. In support of a tumor suppressor function for Plk2, loss of Plk2 increased the formation of lesions in multiparous glands. Collectively, these results demonstrate a novel role for Plk2 in regulating mammary gland development and as a tumor suppressor in mammary tumorigenesis. Disruptions in polarity and mitotic spindle orientation contribute to the progression and evolution of tumorigenesis. However, little is known about the molecular mechanisms regulating these processes in vivo. Here we demonstrate that Polo-like kinase 2 (Plk2) regulates mitotic spindle orientation in the mammary gland and is a putative tumor suppressor. Plk2 is highly expressed in the mammary gland and is required for proper mammary gland development. Loss of Plk2 leads to increased mammary epithelial cell proliferation and ductal hyperbranching. Additionally a novel role for Plk2 in regulating the orientation of the mitotic spindle and maintaining proper cell polarity in the ductal epithelium was discovered. In support of a tumor suppressor function for Plk2, loss of Plk2 increased the formation of lesions in multiparous glands. Collectively, these results demonstrate a novel role for Plk2 in regulating mammary gland development and as a tumor suppressor in mammary tumorigenesis.
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Project description:Transcript profiling was performed by Affymetrix microarray analysis and SAGE to characterize changes in gene expression in the bovine mammary gland in response to 4× versus 2× daily milking during the first week of lactation. These changes in gene expression may contribute to the increased milk production observed in response to increased milking frequency. Our results indicate that increased milking frequency alters expression of genes in the mammary gland related to increased extracellular matrix remodeling, neovascularization, metabolism, cell proliferation and apoptosis. Keywords: Physiological response to stimulus
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2021-06-11 | MSV000087617 | MassIVE
Project description:Pregnancy has been shown to decrease the risk of mammary carcinogenesis in human rretrospective epidemiological studies. In rodents, pregnancy prior to carcinogen administration or after carcinogen challenge has also been shown to reduce the incidence of palpable carcinomas. In this study our objective to determine the underlying genomic signature of the pregnancy and reproductive hormones on the mammary gland that contribute to the protection against mammary gland carcinogenesis. We used the rat microarray technology to observe total transcriptome changes after the pregnancy and exogenous reproductive hormone stimulation of the mammary gland. Fifteen 3 month old post-pubertal virgin Lewis rats were randomly assigned to three groups (5 rats per group): control (C), pregnancy (P) and hormone treatment (H). The P group animals had a full-term pregnancy (21-23 days) and rats in the group H were implanted subcutaneously on the dorsal midline with two silastic capsules [(0.078 inch inner diameter, 0.125 inch outer diameter) x 2 cm long; Dow Corning, Midland, MI) filled separately with 100 μg ethynyl estradiol (Sigma, St. Louis, MO) packed in a cellulose matrix (Sigma) and 30 mg of megesterol acetate (Sigma) for 21 days. The control animals had neither the hormone treatment nor being pregnant. The animals in C and P groups were also implanted with sham capsules filled with cellulose matrix only. The capsules were surgically implanted at the beginning of the experiment and removed from all animals after 21 days except that the capsules were removed from the P group following parturition (21-23 days). The delivered pups in the P group were euthanized within 4-6 hours of delivery to avoid suckling. After the removal of capsules all groups were rested a total of ~49 days before euthanasia. All animals were euthanized during metestrus stage, determined by vaginal cytology and total RNA was extracted from the mammary gland tissues using Trizol reagent.
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