RT Journal Article SR Electronic T1 Mesenchymal stromal cell activation by breast cancer secretomes in bioengineered 3D microenvironments JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e201900304 DO 10.26508/lsa.201900304 VO 2 IS 3 A1 Blache, Ulrich A1 Horton, Edward R A1 Xia, Tian A1 Schoof, Erwin M A1 Blicher, Lene H A1 Schönenberger, Angelina A1 Snedeker, Jess G A1 Martin, Ivan A1 Erler, Janine T A1 Ehrbar, Martin YR 2019 UL http://www.life-science-alliance.org/content/2/3/e201900304.abstract AB 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.