We are analyzing https://link.springer.com/article/10.1186/bcr2755.

Title:
Mapping the cellular and molecular heterogeneity of normal and malignant breast tissues and cultured cell lines | Breast Cancer Research
Description:
Introduction Normal and neoplastic breast tissues are comprised of heterogeneous populations of epithelial cells exhibiting various degrees of maturation and differentiation. While cultured cell lines have been derived from both normal and malignant tissues, it remains unclear to what extent they retain similar levels of differentiation and heterogeneity as that found within breast tissues. Methods We used 12 reduction mammoplasty tissues, 15 primary breast cancer tissues, and 20 human breast epithelial cell lines (16 cancer lines, 4 normal lines) to perform flow cytometry for CD44, CD24, epithelial cell adhesion molecule (EpCAM), and CD49f expression, as well as immunohistochemistry, and in vivo tumor xenograft formation studies to extensively analyze the molecular and cellular characteristics of breast epithelial cell lineages. Results Human breast tissues contain four distinguishable epithelial differentiation states (two luminal phenotypes and two basal phenotypes) that differ on the basis of CD24, EpCAM and CD49f expression. Primary human breast cancer tissues also contain these four cellular states, but in altered proportions compared to normal tissues. In contrast, cultured cancer cell lines are enriched for rare basal and mesenchymal epithelial phenotypes, which are normally present in small numbers within human tissues. Similarly, cultured normal human mammary epithelial cell lines are enriched for rare basal and mesenchymal phenotypes that represent a minor fraction of cells within reduction mammoplasty tissues. Furthermore, although normal human mammary epithelial cell lines exhibit features of bi-potent progenitor cells they are unable to differentiate into mature luminal breast epithelial cells under standard culture conditions. Conclusions As a group breast cancer cell lines represent the heterogeneity of human breast tumors, but individually they exhibit increased lineage-restricted profiles that fall short of truly representing the intratumoral heterogeneity of individual breast tumors. Additionally, normal human mammary epithelial cell lines fail to retain much of the cellular diversity found in human breast tissues and are enriched for differentiation states that are a minority in breast tissues, although they do exhibit features of bi-potent basal progenitor cells. These findings suggest that collections of cell lines representing multiple cell types can be used to model the cellular heterogeneity of tissues.
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cell, cells, breast, lines, luminal, cancer, human, expression, epithelial, basal, tissues, pubmed, tumor, epcam, article, normal, mesenchymal, figure, scholar, tumors, google, differentiation, cdf, mammoplasty, cas, reduction, additional, usa, markers, mammary, flow, staining, primary, epcamcdf, states, culture, tissue, data, cytometry, expressed, cellular, molecular, vimentin, found, files, epcamcdcdf, line, populations, heterogeneity, cultured,

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bi-potent stem/progenitor cells fluorescence-activated cell sorting bi-potent progenitor/stem stem cell-related markers tight cell-cell junctions luminal-type breast cancers basal/mesenchymal-restricted lineage phenotype cellular diversity found pre-existing differentiation state epcam-/cd24-/cd49f+ mesenchymal cells mesenchymal epcam-/cd24-/cd49f+ cells asselin-labat ml bi-potent progenitor cells epcam+/cd24-/cd49f+ cells exhibited breast cancer research epcam+/cd24+/cd49f+ luminal cells epcam+/cd24+/cd49f+ populations compared paraffin-embedded tissue sections showing spindle-cell metaplastic cell line-derived xenografts epcam+/cd24-/cd49f+ basal cells fibroblast specific protein/ib10 epcam+/cd49f+ marker profile α-smooth muscle actin cell surface-based categories luminal epithelium-specific keratins epithelial cells exhibiting immunodeficient nod/scid mice human breast tissue gene expression-based classifiers mammary epithelial cells rat igg2a-pe-cy5 alexa555 conjugated anti-mouse epcam+/locd24-cd49f+ cells adult human breast article download pdf high grade carcinomas human mammary tissues cell stem cell epithelial cell types fully-committed luminal cells epcam-/cd49f+ mesenchymal cells breast cell lines de-identified discarded material primary breast cancers human breast tissues basal/myoepithelial cell enrichment cancer cell lines stem cell hierarchy sorted lineage-depleted cells

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         description:Normal and neoplastic breast tissues are comprised of heterogeneous populations of epithelial cells exhibiting various degrees of maturation and differentiation. While cultured cell lines have been derived from both normal and malignant tissues, it remains unclear to what extent they retain similar levels of differentiation and heterogeneity as that found within breast tissues. We used 12 reduction mammoplasty tissues, 15 primary breast cancer tissues, and 20 human breast epithelial cell lines (16 cancer lines, 4 normal lines) to perform flow cytometry for CD44, CD24, epithelial cell adhesion molecule (EpCAM), and CD49f expression, as well as immunohistochemistry, and in vivo tumor xenograft formation studies to extensively analyze the molecular and cellular characteristics of breast epithelial cell lineages. Human breast tissues contain four distinguishable epithelial differentiation states (two luminal phenotypes and two basal phenotypes) that differ on the basis of CD24, EpCAM and CD49f expression. Primary human breast cancer tissues also contain these four cellular states, but in altered proportions compared to normal tissues. In contrast, cultured cancer cell lines are enriched for rare basal and mesenchymal epithelial phenotypes, which are normally present in small numbers within human tissues. Similarly, cultured normal human mammary epithelial cell lines are enriched for rare basal and mesenchymal phenotypes that represent a minor fraction of cells within reduction mammoplasty tissues. Furthermore, although normal human mammary epithelial cell lines exhibit features of bi-potent progenitor cells they are unable to differentiate into mature luminal breast epithelial cells under standard culture conditions. As a group breast cancer cell lines represent the heterogeneity of human breast tumors, but individually they exhibit increased lineage-restricted profiles that fall short of truly representing the intratumoral heterogeneity of individual breast tumors. Additionally, normal human mammary epithelial cell lines fail to retain much of the cellular diversity found in human breast tissues and are enriched for differentiation states that are a minority in breast tissues, although they do exhibit features of bi-potent basal progenitor cells. These findings suggest that collections of cell lines representing multiple cell types can be used to model the cellular heterogeneity of tissues.
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      affiliation:
            name:Sackler School, Tufts University School of Medicine
            address:
               name:Department of Anatomy & Cellular Biology, Sackler School, Tufts University School of Medicine, Boston, USA
               type:PostalAddress
            type:Organization
            name:Tufts Medical Center
            address:
               name:Molecular Oncology Research Institute, Tufts Medical Center, Boston, USA
               type:PostalAddress
            type:Organization
      name:Hannah Gilmore
      affiliation:
            name:Harvard Medical School
            address:
               name:Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
               type:PostalAddress
            type:Organization
      name:Douglas M Jefferson
      affiliation:
            name:Sackler School, Tufts University School of Medicine
            address:
               name:Department of Physiology, Sackler School, Tufts University School of Medicine, Boston, USA
               type:PostalAddress
            type:Organization
      name:Roger A Graham
      affiliation:
            name:Tufts Medical Center
            address:
               name:Department of Surgery, Tufts Medical Center, Boston, USA
               type:PostalAddress
            type:Organization
      name:Stephen P Naber
      affiliation:
            name:Tufts Medical Center
            address:
               name:Department of Pathology, Tufts Medical Center, Boston, USA
               type:PostalAddress
            type:Organization
      name:Stuart Schnitt
      affiliation:
            name:Harvard Medical School
            address:
               name:Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
               type:PostalAddress
            type:Organization
      name:Charlotte Kuperwasser
      affiliation:
            name:Sackler School, Tufts University School of Medicine
            address:
               name:Department of Anatomy & Cellular Biology, Sackler School, Tufts University School of Medicine, Boston, USA
               type:PostalAddress
            type:Organization
            name:Tufts Medical Center
            address:
               name:Molecular Oncology Research Institute, Tufts Medical Center, Boston, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Anatomy & Cellular Biology, Sackler School, Tufts University School of Medicine, Boston, USA
      name:Molecular Oncology Research Institute, Tufts Medical Center, Boston, USA
      name:Department of Anatomy & Cellular Biology, Sackler School, Tufts University School of Medicine, Boston, USA
      name:Molecular Oncology Research Institute, Tufts Medical Center, Boston, USA
      name:Department of Anatomy & Cellular Biology, Sackler School, Tufts University School of Medicine, Boston, USA
      name:Molecular Oncology Research Institute, Tufts Medical Center, Boston, USA
      name:Department of Anatomy & Cellular Biology, Sackler School, Tufts University School of Medicine, Boston, USA
      name:Molecular Oncology Research Institute, Tufts Medical Center, Boston, USA
      name:Department of Anatomy & Cellular Biology, Sackler School, Tufts University School of Medicine, Boston, USA
      name:Molecular Oncology Research Institute, Tufts Medical Center, Boston, USA
      name:Department of Anatomy & Cellular Biology, Sackler School, Tufts University School of Medicine, Boston, USA
      name:Molecular Oncology Research Institute, Tufts Medical Center, Boston, USA
      name:Department of Anatomy & Cellular Biology, Sackler School, Tufts University School of Medicine, Boston, USA
      name:Molecular Oncology Research Institute, Tufts Medical Center, Boston, USA
      name:Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
      name:Department of Physiology, Sackler School, Tufts University School of Medicine, Boston, USA
      name:Department of Surgery, Tufts Medical Center, Boston, USA
      name:Department of Pathology, Tufts Medical Center, Boston, USA
      name:Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
      name:Department of Anatomy & Cellular Biology, Sackler School, Tufts University School of Medicine, Boston, USA
      name:Molecular Oncology Research Institute, Tufts Medical Center, Boston, USA

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