Deciphering the mammary stem cell niche: a role for laminin-binding integrins
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ABSTRACT:
PROVIDER: PRJNA481124 | ENA |
REPOSITORIES: ENA
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Project description:Integrin dimers a3/b1, a6/b1 and a6/b4 are the receptors of mammary epithelial cells for Laminin, major component of the mammary basement membrane. Antibodies against a6 and a3 integrin chains serve to isolate stem cell enriched populations from mammary epithelium, however, role of integrin dimers comprising these chains in the control of mammary stem cell activity are not known. To investigate the role of Laminin-binding integrins in the control of mammary stem cell function, a3 and a6 chains were deleted from mammary basal cells in vitro using Cre-recombinase carrying adenovirus. We found that deletion of single integrin chain (either a3, or a6) did not significantly affect stem cell potential as evaluated by transplantation and mammosphere assays, whereas basal cells depleted of both a3 and a6 integrin chains (a3a6KO) presented severely diminished stem cell activity. In this study the transcriptional profiles of a3a6KO were analysed and compared to those of control cells.
2019-04-23 | GSE117120 | GEO
Project description:Integrin dimers α3/β1, α6/β1 and α6/β4 are the mammary epithelial cell receptors for laminins, which are major components of the basement membrane, a specialized extracellular matrix surrounding the mammary epithelium. The roles of specific basement membrane components and their integrin receptors in the regulation of functional gland development have not been analyzed in detail. To investigate the functions of laminin-binding integrins, we obtained mutant mice with mammary luminal cell-specific deficiencies of the α3 and α6 integrin chains generated by the Cre-Lox approach. During pregnancy, mutant mice displayed low levels of luminal progenitor activity and retarded lobulo-alveolar development, whereas their mammary glands seemed to be functional at the onset of lactation. Myoepithelial cell morphology was markedly altered in mutant glands, suggesting cellular compensation mechanisms involving cytoskeleton reorganization. However, lactation was not sustained in mutant mice, and the glands underwent precocious involution. Inactivation of the p53 gene rescued the growth defects but did not restore lactogenesis in mutant mice. This study reveals an essential role for laminin-binding integrins in functional mammary gland development.
2020-02-04 | GSE132281 | GEO
Project description:Integrin dimers α3/β1, α6/β1 and α6/β4 are the mammary epithelial cell receptors for laminins, which are major components of the basement membrane, a specialized extracellular matrix surrounding the mammary epithelium. The roles of specific basement membrane components and their integrin receptors in the regulation of functional gland development have not been analyzed in detail. To investigate the functions of laminin-binding integrins, we obtained mutant mice with mammary luminal cell-specific deficiencies of the α3 and α6 integrin chains generated by the Cre-Lox approach. During pregnancy, mutant mice displayed low levels of luminal progenitor activity and retarded lobulo-alveolar development, whereas their mammary glands seemed to be functional at the onset of lactation. Myoepithelial cell morphology was markedly altered in mutant glands, suggesting cellular compensation mechanisms involving cytoskeleton reorganization. However, lactation was not sustained in mutant mice, and the glands underwent precocious involution. Inactivation of the p53 gene rescued the growth defects but did not restore lactogenesis in mutant mice. This study reveals an essential role for laminin-binding integrins in functional mammary gland development.
2020-02-04 | GSE132349 | GEO
Project description: Not available
| S-EPMC6450809 | biostudies-literature
Project description:Mammary epithelium is composed by luminal and basal epithelial cells, which are adhere to the basement membrane (BM). To dissect how basal cell functions are regulated by BM laminin adhesion, we performed RNA sequencing of basal human mammary epithelial cells adhered on laminin-111, -421 or -521 coated cell culture plates for 48 hours.
2022-11-07 | GSE197950 | GEO
Project description:Stephen Paget first proposed, in 1889, that organ distribution of metastases is a non-random event, yet metastatic organotropism remains one of the greatest mysteries in cancer biology. Here, we demonstrate that exosomes released by lung-, liver- and brain-tropic tumor cells fuse preferentially with resident cells at their predicted destination, such as fibroblasts and epithelial cells in the lung, Kupffer cells in the liver, and endothelial cells in the brain. We found that exosome homing to organ-specific cell types prepares the pre-metastatic niche and that treatment with exosomes derived from lung tropic models can redirect metastasis to the lung. Proteomic profiling of exosomes revealed distinct integrin expression patterns associated with each organ-specific metastasis. Whereas exosomal integrins α6β4 and α6β1 were associated with lung metastasis, exosomal integrins αvβ5 and αvβ3 were linked with liver and brain metastases, respectively. Targeting α6β4 and αvβ5 integrins decreased exosome uptake and metastasis in the lung and liver, respectively. Importantly, we demonstrate that exosome uptake activates a cell-specific subset of S100 family genes, known to support cell migration and niche formation. Finally, our clinical data indicate that integrin-expression profiles in circulating plasma exosomes from cancer patients could be used to predict organ-specific metastasis. Education of human von Kupffer cells in vitro with human pancreatic cancer exosomes
2015-06-17 | E-GEOD-68919 | biostudies-arrayexpress
Project description:Laminin-binding integrins are essential for the maintenance of functional secretory epithelium in lactation
| PRJNA547508 | ENA
Project description:Stephen Paget first proposed, in 1889, that organ distribution of metastases is a non-random event, yet metastatic organotropism remains one of the greatest mysteries in cancer biology. Here, we demonstrate that exosomes released by lung-, liver- and brain-tropic tumor cells fuse preferentially with resident cells at their predicted destination, such as fibroblasts and epithelial cells in the lung, Kupffer cells in the liver, and endothelial cells in the brain. We found that exosome homing to organ-specific cell types prepares the pre-metastatic niche and that treatment with exosomes derived from lung tropic models can redirect metastasis to the lung. Proteomic profiling of exosomes revealed distinct integrin expression patterns associated with each organ-specific metastasis. Whereas exosomal integrins α6β4 and α6β1 were associated with lung metastasis, exosomal integrins αvβ5 and αvβ3 were linked with liver and brain metastases, respectively. Targeting α6β4 and αvβ5 integrins decreased exosome uptake and metastasis in the lung and liver, respectively. Importantly, we demonstrate that exosome uptake activates a cell-specific subset of S100 family genes, known to support cell migration and niche formation. Finally, our clinical data indicate that integrin-expression profiles in circulating plasma exosomes from cancer patients could be used to predict organ-specific metastasis.
2015-06-17 | GSE68919 | GEO
Project description:Laminin-binding integrins are essential for the maintenance of functional secretory epithelium in lactation [luminal cells]
| PRJNA547672 | ENA
Project description:A goal of this project is to evaluate the integrin mRNA expression in human neural stem/progenitor cells (hNSPC) using high-throughput sequencing technologies. We found high levels of mRNA expression for the β1, α7, α3, α6, β5, αV, α5, and α9 integrins. This suggests that hNSPCs may express integrin receptors that can bind fibrinogen and laminin proteins.
2016-12-14 | GSE76011 | GEO