1. Cancer Biology
  2. Immunology and Inflammation
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Osterix-Cre marks distinct subsets of CD45- and CD45+ stromal populations in extra-skeletal tumors with pro-tumorigenic characteristics

  1. Biancamaria Ricci
  2. Eric Tycksen
  3. Hamza Celik
  4. Jad I Belle
  5. Francesca Fontana
  6. Roberto Civitelli
  7. Roberta Faccio  Is a corresponding author
  1. Washington University in St Louis, United States
Research Article
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Cite this article as: eLife 2020;9:e54659 doi: 10.7554/eLife.54659

Abstract

Cancer-associated fibroblasts (CAFs) are a heterogeneous population of mesenchymal cells supporting tumor progression, whose origin remains to be fully elucidated. Osterix (Osx) is a marker of osteogenic differentiation, expressed in skeletal progenitor stem cells and bone-forming osteoblasts. We report Osx expression in CAFs and by using Osx-cre;TdTomato reporter mice we confirm the presence and pro-tumorigenic function of TdTOSX+ cells in extra-skeletal tumors. Surprisingly, only a minority of TdTOSX+ cells expresses fibroblast and osteogenic markers. The majority of TdTOSX+ cells express the hematopoietic marker CD45, have a genetic and phenotypic profile resembling that of tumor infiltrating myeloid and lymphoid populations, but with higher expression of lymphocytic immune suppressive genes. We find Osx transcript and Osx protein expression early during hematopoiesis, in subsets of hematopoietic stem cells and multipotent progenitor populations. Our results indicate that Osx marks distinct tumor promoting CD45- and CD45+ populations and challenge the dogma that Osx is expressed exclusively in cells of mesenchymal origin.

Article and author information

Author details

  1. Biancamaria Ricci

    Orthopedics, Washington University in St Louis, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1574-6043
  2. Eric Tycksen

    Genetics, Washington University in St Louis, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Hamza Celik

    Internal Medicine, Washington University in St Louis, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jad I Belle

    Medicine, Washington University in St Louis, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Francesca Fontana

    Internal Medicine, Washington University in St Louis, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Roberto Civitelli

    Internal Medicine, Washington University in St Louis, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4076-4315
  7. Roberta Faccio

    Orthopedics, Washington University in St Louis, St. Louis, United States
    For correspondence
    faccior@wustl.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1639-2005

Funding

National Institutes of Health (R01 CA235096)

  • Roberta Faccio

National Institutes of Health (R01 AR066551)

  • Roberta Faccio

Shriners Hospital (P19-07408CR)

  • Roberta Faccio

Siteman Cancer Center

  • Roberto Civitelli
  • Roberta Faccio

JIT Award by Washinghton University Institute for Clinical and Translational Sciences (TR000448)

  • Francesca Fontana
  • Roberto Civitelli

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All the animals were handled according to the Institutional Animal Care and Use Committee (IACUC) protocols (#2016-0228 and # 2019-0982 to RF, #2014-0279 and #2017-0095 to RC).

Reviewing Editor

  1. Ivo Kalajzic, UConn Health, United States

Publication history

  1. Received: December 21, 2019
  2. Accepted: July 27, 2020
  3. Accepted Manuscript published: August 5, 2020 (version 1)
  4. Version of Record published: August 14, 2020 (version 2)

Copyright

© 2020, Ricci et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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