Header

UZH-Logo

Maintenance Infos

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


Blache, Ulrich; Horton, Edward R; Xia, Tian; Schoof, Erwin M; Blicher, Lene H; Schönenberger, Angelina; Snedeker, Jess G; Martin, Ivan; Erler, Janine T; Ehrbar, Martin (2019). Mesenchymal stromal cell activation by breast cancer secretomes in bioengineered 3D microenvironments. Life Science Alliance, 2(3):e201900304.

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.

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.

Statistics

Citations

Dimensions.ai Metrics

Altmetrics

Downloads

8 downloads since deposited on 07 Feb 2020
8 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Obstetrics
04 Faculty of Medicine > Balgrist University Hospital, Swiss Spinal Cord Injury Center
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:June 2019
Deposited On:07 Feb 2020 16:23
Last Modified:01 Mar 2020 14:46
Publisher:Life Science Alliance
ISSN:2575-1077
OA Status:Green
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.26508/lsa.201900304
PubMed ID:31160380

Download

Green Open Access

Download PDF  'Mesenchymal stromal cell activation by breast cancer secretomes in bioengineered 3D microenvironments'.
Preview
Content: Published Version
Language: English
Filetype: PDF
Size: 3MB
View at publisher
Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)