Evidence of two distinct functionally specialized fibroblast lineages in breast stroma

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Evidence of two distinct functionally specialized fibroblast lineages in breast stroma. / Morsing, Mikkel; Klitgaard, Marie Christine; Jafari Kermani, Abbas; Villadsen, Rene; Kassem, Moustapha Saad El-Deen; Petersen, Ole William; Rønnov-Jessen, Lone.

In: Breast Cancer Research (Online), Vol. 18, 108, 2016.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Morsing, M, Klitgaard, MC, Jafari Kermani, A, Villadsen, R, Kassem, MSE-D, Petersen, OW & Rønnov-Jessen, L 2016, 'Evidence of two distinct functionally specialized fibroblast lineages in breast stroma', Breast Cancer Research (Online), vol. 18, 108. https://doi.org/10.1186/s13058-016-0769-2

APA

Morsing, M., Klitgaard, M. C., Jafari Kermani, A., Villadsen, R., Kassem, M. S. E-D., Petersen, O. W., & Rønnov-Jessen, L. (2016). Evidence of two distinct functionally specialized fibroblast lineages in breast stroma. Breast Cancer Research (Online), 18, [108]. https://doi.org/10.1186/s13058-016-0769-2

Vancouver

Morsing M, Klitgaard MC, Jafari Kermani A, Villadsen R, Kassem MSE-D, Petersen OW et al. Evidence of two distinct functionally specialized fibroblast lineages in breast stroma. Breast Cancer Research (Online). 2016;18. 108. https://doi.org/10.1186/s13058-016-0769-2

Author

Morsing, Mikkel ; Klitgaard, Marie Christine ; Jafari Kermani, Abbas ; Villadsen, Rene ; Kassem, Moustapha Saad El-Deen ; Petersen, Ole William ; Rønnov-Jessen, Lone. / Evidence of two distinct functionally specialized fibroblast lineages in breast stroma. In: Breast Cancer Research (Online). 2016 ; Vol. 18.

Bibtex

@article{9262a093eed94b4c9f102ca60976fd15,
title = "Evidence of two distinct functionally specialized fibroblast lineages in breast stroma",
abstract = "BackgroundThe terminal duct lobular unit (TDLU) is the most dynamic structure in the human breast and the putative site of origin of human breast cancer. Although stromal cells contribute to a specialized microenvironment in many organs, this component remains largely understudied in the human breast. We here demonstrate the impact on epithelium of two lineages of breast stromal fibroblasts, one of which accumulates in the TDLU while the other resides outside the TDLU in the interlobular stroma.MethodsThe two lineages are prospectively isolated by fluorescence activated cell sorting (FACS) based on different expression levels of CD105 and CD26. The characteristics of the two fibroblast lineages are assessed by immunocytochemical staining and gene expression analysis. The differentiation capacity of the two fibroblast populations is determined by exposure to specific differentiating conditions followed by analysis of adipogenic and osteogenic differentiation. To test whether the two fibroblast lineages are functionally imprinted by their site of origin, single cell sorted CD271low/MUC1high normal breast luminal epithelial cells are plated on fibroblast feeders for the observation of morphological development. Epithelial structure formation and polarization is shown by immunofluorescence and digitalized quantification of immunoperoxidase-stained cultures.ResultsLobular fibroblasts are CD105high/CD26low while interlobular fibroblasts are CD105low/CD26high. Once isolated the two lineages remain phenotypically stable and functionally distinct in culture. Lobular fibroblasts have properties in common with bone marrow derived mesenchymal stem cells and they specifically convey growth and branching morphogenesis of epithelial progenitors.ConclusionsTwo distinct functionally specialized fibroblast lineages exist in the normal human breast, of which the lobular fibroblasts have properties in common with mesenchymal stem cells and support epithelial growth and morphogenesis. We propose that lobular fibroblasts constitute a specialized microenvironment for human breast luminal epithelial progenitors, i.e. the putative precursors of breast cancer.",
keywords = "Breast, Epithelial morphogenesis, Fibroblasts, Mesenchymal stem cells",
author = "Mikkel Morsing and Klitgaard, {Marie Christine} and {Jafari Kermani}, Abbas and Rene Villadsen and Kassem, {Moustapha Saad El-Deen} and Petersen, {Ole William} and Lone R{\o}nnov-Jessen",
year = "2016",
doi = "10.1186/s13058-016-0769-2",
language = "English",
volume = "18",
journal = "Breast Cancer Research",
issn = "1465-5411",
publisher = "BioMed Central Ltd.",

}

RIS

TY - JOUR

T1 - Evidence of two distinct functionally specialized fibroblast lineages in breast stroma

AU - Morsing, Mikkel

AU - Klitgaard, Marie Christine

AU - Jafari Kermani, Abbas

AU - Villadsen, Rene

AU - Kassem, Moustapha Saad El-Deen

AU - Petersen, Ole William

AU - Rønnov-Jessen, Lone

PY - 2016

Y1 - 2016

N2 - BackgroundThe terminal duct lobular unit (TDLU) is the most dynamic structure in the human breast and the putative site of origin of human breast cancer. Although stromal cells contribute to a specialized microenvironment in many organs, this component remains largely understudied in the human breast. We here demonstrate the impact on epithelium of two lineages of breast stromal fibroblasts, one of which accumulates in the TDLU while the other resides outside the TDLU in the interlobular stroma.MethodsThe two lineages are prospectively isolated by fluorescence activated cell sorting (FACS) based on different expression levels of CD105 and CD26. The characteristics of the two fibroblast lineages are assessed by immunocytochemical staining and gene expression analysis. The differentiation capacity of the two fibroblast populations is determined by exposure to specific differentiating conditions followed by analysis of adipogenic and osteogenic differentiation. To test whether the two fibroblast lineages are functionally imprinted by their site of origin, single cell sorted CD271low/MUC1high normal breast luminal epithelial cells are plated on fibroblast feeders for the observation of morphological development. Epithelial structure formation and polarization is shown by immunofluorescence and digitalized quantification of immunoperoxidase-stained cultures.ResultsLobular fibroblasts are CD105high/CD26low while interlobular fibroblasts are CD105low/CD26high. Once isolated the two lineages remain phenotypically stable and functionally distinct in culture. Lobular fibroblasts have properties in common with bone marrow derived mesenchymal stem cells and they specifically convey growth and branching morphogenesis of epithelial progenitors.ConclusionsTwo distinct functionally specialized fibroblast lineages exist in the normal human breast, of which the lobular fibroblasts have properties in common with mesenchymal stem cells and support epithelial growth and morphogenesis. We propose that lobular fibroblasts constitute a specialized microenvironment for human breast luminal epithelial progenitors, i.e. the putative precursors of breast cancer.

AB - BackgroundThe terminal duct lobular unit (TDLU) is the most dynamic structure in the human breast and the putative site of origin of human breast cancer. Although stromal cells contribute to a specialized microenvironment in many organs, this component remains largely understudied in the human breast. We here demonstrate the impact on epithelium of two lineages of breast stromal fibroblasts, one of which accumulates in the TDLU while the other resides outside the TDLU in the interlobular stroma.MethodsThe two lineages are prospectively isolated by fluorescence activated cell sorting (FACS) based on different expression levels of CD105 and CD26. The characteristics of the two fibroblast lineages are assessed by immunocytochemical staining and gene expression analysis. The differentiation capacity of the two fibroblast populations is determined by exposure to specific differentiating conditions followed by analysis of adipogenic and osteogenic differentiation. To test whether the two fibroblast lineages are functionally imprinted by their site of origin, single cell sorted CD271low/MUC1high normal breast luminal epithelial cells are plated on fibroblast feeders for the observation of morphological development. Epithelial structure formation and polarization is shown by immunofluorescence and digitalized quantification of immunoperoxidase-stained cultures.ResultsLobular fibroblasts are CD105high/CD26low while interlobular fibroblasts are CD105low/CD26high. Once isolated the two lineages remain phenotypically stable and functionally distinct in culture. Lobular fibroblasts have properties in common with bone marrow derived mesenchymal stem cells and they specifically convey growth and branching morphogenesis of epithelial progenitors.ConclusionsTwo distinct functionally specialized fibroblast lineages exist in the normal human breast, of which the lobular fibroblasts have properties in common with mesenchymal stem cells and support epithelial growth and morphogenesis. We propose that lobular fibroblasts constitute a specialized microenvironment for human breast luminal epithelial progenitors, i.e. the putative precursors of breast cancer.

KW - Breast

KW - Epithelial morphogenesis

KW - Fibroblasts

KW - Mesenchymal stem cells

U2 - 10.1186/s13058-016-0769-2

DO - 10.1186/s13058-016-0769-2

M3 - Journal article

C2 - 27809866

VL - 18

JO - Breast Cancer Research

JF - Breast Cancer Research

SN - 1465-5411

M1 - 108

ER -

ID: 169443327