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We are analyzing https://link.springer.com/article/10.1186/bcr2218.

Title:
Novel multicellular organotypic models of normal and malignant breast: tools for dissecting the role of the microenvironment in breast cancer progression | Breast Cancer Research
Description:
Introduction There is increasing recognition of the role of the microenvironment in the control of both normal and tumour cell behaviour. In the breast, myoepithelial cells and fibroblasts can influence tumour cell behaviour, with myoepithelial cells exhibiting a broad tumour-suppressor activity while fibroblasts frequently promote tumour growth and invasion. This study describes the development of physiologically relevant three-dimensional heterotypic culture systems containing mixed normal or tumour-derived breast populations and shows how such models can be used to dissect the interactions that influence cell behaviour. Methods Populations of luminal cells, myoepithelial cells and fibroblasts were isolated from normal and malignant breast tissue, characterised and compared with immortalised cell lines. Co-localisation of normal and malignant luminal cells with myoepithelial cells alone or with either normal or tumour-derived fibroblasts was studied. Cultures were grown for seven days, and then gels were fixed and whole gel immunofluorescence carried out to assess co-localisation and polarisation. The potential role of matrix metalloproteinases (MMP) or hepatocyte growth factor(HGF)-c-met signalling in disrupting cellular organisation was investigated by incorporating inhibitors into cultures either alone or in combination. Results Over a culture period of seven days, myoepithelial cells organised themselves around luminal cell populations forming dual-cell co-units. Characterisation of co-units showed established basal polarity and differentiation analogous to their in vivo counterparts. Tumour cell co-units revealed subtle differences to normal co-units including disruption of basement membrane and loss of β4-integrin, as described in ductal carcinoma in situ (DCIS) in vivo. Inclusion of normal fibroblasts had no influence on co-unit formation; however, inclusion of tumour-associated fibroblasts lead to disruption of co-unit organisation, and this was significantly inhibited in the presence of MMP and/or c-met inhibitors. Conclusions To the best of the authors
Website Age:
28 years and 1 months (reg. 1997-05-29).

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🌠 Phenomenal Traffic: 5M - 10M visitors per month


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Keywords {🔍}

cells, cell, myoepithelial, breast, luminal, normal, fibroblasts, counits, cancer, populations, figure, pubmed, article, expression, google, scholar, fibroblast, tumour, epithelial, primary, cas, cultures, counit, membrane, mmp, population, role, mcf, basement, human, media, isolated, tissue, βintegrin, presence, inhibitor, models, formation, shown, microenvironment, culture, lines, model, tafs, expressed, interactions, organisation, carcinoma, authors, ema,

Topics {✒️}

poly-l-lysine coated coverslips professor mike o'hare transforming growth factor-beta hepatocyte growth factor elevated sdf-1/cxcl12 secretion α-smooth muscle actin α–smooth muscle actin received pre-operative chemotherapy cell migration analyses regulate hgf-induced invasion article download pdf growth factor requirements cr-uk clinical centre completely animal-free environment human epithelial-carcinoma cells pre-invasive breast disease urokinase-type-plasminogen-activator broad tumour-suppressor activity o'hare mj tumour-derived breast populations stromal-derived mmp members unravel myoepithelial-luminal interactions breast cancer invasion mcf7/myoepithelial/taf cultures epithelial membrane antigen pre-aggregated mcf-7 cells cells expressed α-sma hgf-c-met interactions luminal-myoepithelial cell cultures privacy choices/manage cookies full size image related subjects c-met/hgf receptor o'connell jt authors’ original file streuli ch mammary epithelial differentiation human breast duct epithelial-stromal interactions present human breast cells broad spectrum inhibitor exhibited identical patterns myoepithelial cell line human breast carcinoma invasive ductal carcinomas article number r3 breast cancer cells 2mm l-glutamine low power image urokinase plasminogen activator

Schema {🗺️}

WebPage:
      mainEntity:
         headline:Novel multicellular organotypic models of normal and malignant breast: tools for dissecting the role of the microenvironment in breast cancer progression
         description:There is increasing recognition of the role of the microenvironment in the control of both normal and tumour cell behaviour. In the breast, myoepithelial cells and fibroblasts can influence tumour cell behaviour, with myoepithelial cells exhibiting a broad tumour-suppressor activity while fibroblasts frequently promote tumour growth and invasion. This study describes the development of physiologically relevant three-dimensional heterotypic culture systems containing mixed normal or tumour-derived breast populations and shows how such models can be used to dissect the interactions that influence cell behaviour. Populations of luminal cells, myoepithelial cells and fibroblasts were isolated from normal and malignant breast tissue, characterised and compared with immortalised cell lines. Co-localisation of normal and malignant luminal cells with myoepithelial cells alone or with either normal or tumour-derived fibroblasts was studied. Cultures were grown for seven days, and then gels were fixed and whole gel immunofluorescence carried out to assess co-localisation and polarisation. The potential role of matrix metalloproteinases (MMP) or hepatocyte growth factor(HGF)-c-met signalling in disrupting cellular organisation was investigated by incorporating inhibitors into cultures either alone or in combination. Over a culture period of seven days, myoepithelial cells organised themselves around luminal cell populations forming dual-cell co-units. Characterisation of co-units showed established basal polarity and differentiation analogous to their in vivo counterparts. Tumour cell co-units revealed subtle differences to normal co-units including disruption of basement membrane and loss of β4-integrin, as described in ductal carcinoma in situ (DCIS) in vivo. Inclusion of normal fibroblasts had no influence on co-unit formation; however, inclusion of tumour-associated fibroblasts lead to disruption of co-unit organisation, and this was significantly inhibited in the presence of MMP and/or c-met inhibitors. To the best of the authors' knowledge, this study describes for the first time a co-culture model comprising three major components of normal and malignant breast: luminal cells, myoepithelial cells and stromal fibroblasts. These cells organise into structures recapitulating normal and DCIS breast, with homing of myoepithelial cells around the luminal population. Importantly, differences are exhibited between these systems reflecting those described in tissues, including a central role for tumour-associated fibroblasts and MMPs in mediating disruption of normal structures. These findings support the value of these models in dissecting normal and tumour cell behaviour in an appropriate microenvironment.
         datePublished:2009-01-19T00:00:00Z
         dateModified:2009-01-19T00:00:00Z
         pageStart:1
         pageEnd:11
         license:http://creativecommons.org/licenses/by/2.0/
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         keywords:
            Hepatocyte Growth Factor
            Myoepithelial Cell
            Epithelial Membrane Antigen
            Luminal Cell
            Normal Fibroblast
            Cancer Research
            Oncology
            Surgical Oncology
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      headline:Novel multicellular organotypic models of normal and malignant breast: tools for dissecting the role of the microenvironment in breast cancer progression
      description:There is increasing recognition of the role of the microenvironment in the control of both normal and tumour cell behaviour. In the breast, myoepithelial cells and fibroblasts can influence tumour cell behaviour, with myoepithelial cells exhibiting a broad tumour-suppressor activity while fibroblasts frequently promote tumour growth and invasion. This study describes the development of physiologically relevant three-dimensional heterotypic culture systems containing mixed normal or tumour-derived breast populations and shows how such models can be used to dissect the interactions that influence cell behaviour. Populations of luminal cells, myoepithelial cells and fibroblasts were isolated from normal and malignant breast tissue, characterised and compared with immortalised cell lines. Co-localisation of normal and malignant luminal cells with myoepithelial cells alone or with either normal or tumour-derived fibroblasts was studied. Cultures were grown for seven days, and then gels were fixed and whole gel immunofluorescence carried out to assess co-localisation and polarisation. The potential role of matrix metalloproteinases (MMP) or hepatocyte growth factor(HGF)-c-met signalling in disrupting cellular organisation was investigated by incorporating inhibitors into cultures either alone or in combination. Over a culture period of seven days, myoepithelial cells organised themselves around luminal cell populations forming dual-cell co-units. Characterisation of co-units showed established basal polarity and differentiation analogous to their in vivo counterparts. Tumour cell co-units revealed subtle differences to normal co-units including disruption of basement membrane and loss of β4-integrin, as described in ductal carcinoma in situ (DCIS) in vivo. Inclusion of normal fibroblasts had no influence on co-unit formation; however, inclusion of tumour-associated fibroblasts lead to disruption of co-unit organisation, and this was significantly inhibited in the presence of MMP and/or c-met inhibitors. To the best of the authors' knowledge, this study describes for the first time a co-culture model comprising three major components of normal and malignant breast: luminal cells, myoepithelial cells and stromal fibroblasts. These cells organise into structures recapitulating normal and DCIS breast, with homing of myoepithelial cells around the luminal population. Importantly, differences are exhibited between these systems reflecting those described in tissues, including a central role for tumour-associated fibroblasts and MMPs in mediating disruption of normal structures. These findings support the value of these models in dissecting normal and tumour cell behaviour in an appropriate microenvironment.
      datePublished:2009-01-19T00:00:00Z
      dateModified:2009-01-19T00:00:00Z
      pageStart:1
      pageEnd:11
      license:http://creativecommons.org/licenses/by/2.0/
      sameAs:https://doi.org/10.1186/bcr2218
      keywords:
         Hepatocyte Growth Factor
         Myoepithelial Cell
         Epithelial Membrane Antigen
         Luminal Cell
         Normal Fibroblast
         Cancer Research
         Oncology
         Surgical Oncology
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                  name:Queen Mary's School of Medicine and Dentistry, John Vane Science Centre
                  address:
                     name:Centre for Tumour Biology, Institute of Cancer and CR-UK Clinical Centre, Bart's and The London, Queen Mary's School of Medicine and Dentistry, John Vane Science Centre, London, UK
                     type:PostalAddress
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            type:Person
            name:Linda A Gordon
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                  name:Queen Mary's School of Medicine and Dentistry, John Vane Science Centre
                  address:
                     name:Centre for Tumour Biology, Institute of Cancer and CR-UK Clinical Centre, Bart's and The London, Queen Mary's School of Medicine and Dentistry, John Vane Science Centre, London, UK
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      affiliation:
            name:Queen Mary's School of Medicine and Dentistry, John Vane Science Centre
            address:
               name:Centre for Tumour Biology, Institute of Cancer and CR-UK Clinical Centre, Bart's and The London, Queen Mary's School of Medicine and Dentistry, John Vane Science Centre, London, UK
               type:PostalAddress
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      name:Kellie T Brouilette
      affiliation:
            name:University College London
            address:
               name:Prostate Cancer Research Centre, Department of Surgery, University College London, London, UK
               type:PostalAddress
            type:Organization
      name:Anja Markert
      affiliation:
            name:Queen Mary's School of Medicine and Dentistry, John Vane Science Centre
            address:
               name:Centre for Tumour Biology, Institute of Cancer and CR-UK Clinical Centre, Bart's and The London, Queen Mary's School of Medicine and Dentistry, John Vane Science Centre, London, UK
               type:PostalAddress
            type:Organization
      name:Linda A Gordon
      affiliation:
            name:Queen Mary's School of Medicine and Dentistry, John Vane Science Centre
            address:
               name:Centre for Tumour Biology, Institute of Cancer and CR-UK Clinical Centre, Bart's and The London, Queen Mary's School of Medicine and Dentistry, John Vane Science Centre, London, UK
               type:PostalAddress
            type:Organization
      name:J Louise Jones
      affiliation:
            name:Queen Mary's School of Medicine and Dentistry, John Vane Science Centre
            address:
               name:Centre for Tumour Biology, Institute of Cancer and CR-UK Clinical Centre, Bart's and The London, Queen Mary's School of Medicine and Dentistry, John Vane Science Centre, London, UK
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Centre for Tumour Biology, Institute of Cancer and CR-UK Clinical Centre, Bart's and The London, Queen Mary's School of Medicine and Dentistry, John Vane Science Centre, London, UK
      name:Prostate Cancer Research Centre, Department of Surgery, University College London, London, UK
      name:Centre for Tumour Biology, Institute of Cancer and CR-UK Clinical Centre, Bart's and The London, Queen Mary's School of Medicine and Dentistry, John Vane Science Centre, London, UK
      name:Centre for Tumour Biology, Institute of Cancer and CR-UK Clinical Centre, Bart's and The London, Queen Mary's School of Medicine and Dentistry, John Vane Science Centre, London, UK
      name:Centre for Tumour Biology, Institute of Cancer and CR-UK Clinical Centre, Bart's and The London, Queen Mary's School of Medicine and Dentistry, John Vane Science Centre, London, UK

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