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Mesenchymal stromal cell activation by breast cancer secretomes in bioengineered 3D microenvironments

View ORCID ProfileUlrich Blache, View ORCID ProfileEdward R Horton, Tian Xia, Erwin M Schoof, Lene H Blicher, Angelina Schönenberger, Jess G Snedeker, Ivan Martin, Janine T Erler  Correspondence email, View ORCID ProfileMartin Ehrbar  Correspondence email
Ulrich Blache
1Department of Obstetrics, University and University Hospital of Zurich, Zurich, Switzerland
2Institute for Biomechanics, Eidgenössische Technische Hochschule Zurich, Zurich, Switzerland
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  • ORCID record for Ulrich Blache
Edward R Horton
3Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark
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Tian Xia
3Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark
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Erwin M Schoof
4Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark
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Lene H Blicher
4Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark
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Angelina Schönenberger
2Institute for Biomechanics, Eidgenössische Technische Hochschule Zurich, Zurich, Switzerland
5Biomechanics Laboratory, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
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Jess G Snedeker
2Institute for Biomechanics, Eidgenössische Technische Hochschule Zurich, Zurich, Switzerland
5Biomechanics Laboratory, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
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Ivan Martin
6Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
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Janine T Erler
3Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark
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  • For correspondence: janine.erler@bric.ku.dk
Martin Ehrbar
1Department of Obstetrics, University and University Hospital of Zurich, Zurich, Switzerland
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  • For correspondence: martin.ehrbar@usz.ch
Published 3 June 2019. DOI: 10.26508/lsa.201900304
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Abstract

Mesenchymal stromal cells (MSCs) are key contributors of the tumour microenvironment and are known to promote cancer progression through reciprocal communication with cancer cells, but how they become activated is not fully understood. Here, we investigate how breast cancer cells from different stages of the metastatic cascade convert MSCs into tumour-associated MSCs (TA-MSCs) using unbiased, global approaches. Using mass spectrometry, we compared the secretomes of MCF-7 cells, invasive MDA-MB-231 cells, and sublines isolated from bone, lung, and brain metastases and identified ECM and exosome components associated with invasion and organ-specific metastasis. Next, we used synthetic hydrogels to investigate how these different secretomes activate MSCs in bioengineered 3D microenvironments. Using kinase activity profiling and RNA sequencing, we found that only MDA-MB-231 breast cancer secretomes convert MSCs into TA-MSCs, resulting in an immunomodulatory phenotype that was particularly prominent in response to bone-tropic cancer cells. We have investigated paracrine signalling from breast cancer cells to TA-MSCs in 3D, which may highlight new potential targets for anticancer therapy approaches aimed at targeting tumour stroma.

  • Received January 14, 2019.
  • Revision received May 22, 2019.
  • Accepted May 22, 2019.
  • © 2019 Blache et al.
Creative Commons logoCreative Commons logohttps://creativecommons.org/licenses/by/4.0/

This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).

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MSC activation by cancer secretomes in 3D
Ulrich Blache, Edward R Horton, Tian Xia, Erwin M Schoof, Lene H Blicher, Angelina Schönenberger, Jess G Snedeker, Ivan Martin, Janine T Erler, Martin Ehrbar
Life Science Alliance Jun 2019, 2 (3) e201900304; DOI: 10.26508/lsa.201900304

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MSC activation by cancer secretomes in 3D
Ulrich Blache, Edward R Horton, Tian Xia, Erwin M Schoof, Lene H Blicher, Angelina Schönenberger, Jess G Snedeker, Ivan Martin, Janine T Erler, Martin Ehrbar
Life Science Alliance Jun 2019, 2 (3) e201900304; DOI: 10.26508/lsa.201900304
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Volume 2, No. 3
June 2019
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