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Understanding the ECM's role in EMT can uncover new therapeutic targets, yet replicating these interactions in vitro remains challenging. It is shown that hybrid hydrogels of alginate (ALG) and cell\u2010derived decellularized ECM (dECM), with independently tunable composition and stiffness, are useful 3D\u2010models to explore the impact of the breast tumor matrix on EMT. Soft RGD\u2010ALG hydrogels (200\u00a0Pa), used as neutral bulk material, supported mammary epithelial cells morphogenesis without spontaneous EMT, allowing to define the gene, protein, and biochemical profiles of cells at different TGF\u03b21\u2010induced EMT states. To mimic the breast tumor composition, dECM from TGF\u03b21\u2010activated fibroblasts (adECM) are generated, which shows upregulation of tumor\u2010associated proteins compared to ndECM from normal fibroblasts. Using hybrid adECM\u2010ALG hydrogels, it is shown that the presence of adECM induces partial EMT in normal epithelial cells, and amplifes TGF\u2010\u03b21 effects compared to ALG and ndECM\u2010ALG. Increasing the hydrogel stiffness to tumor\u2010like levels (2.5\u00a0kPa) have a synergistic effect, promoting a more evident EMT. These findings shed light on the complex interplay between matrix composition and stiffness in EMT, underscoring the utility of dECM\u2010ALG hydrogels as a valuable in vitro platform for cancer research.<\/jats:p>","DOI":"10.1002\/adhm.202401032","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T03:40:49Z","timestamp":1725853249000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Tunable Hybrid Hydrogels of Alginate and Cell\u2010Derived dECM to Study the Impact of Matrix Alterations on Epithelial\u2010to\u2010Mesenchymal Transition"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0306-5259","authenticated-orcid":false,"given":"P.","family":"Barros da Silva","sequence":"first","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto  Rua Alfredo Allen 208 Porto 4200\u2010135 Portugal"},{"name":"INEB \u2013 Instituto de Engenharia Biom\u00e9dica Universidade do Porto  Porto 4200\u2010135 Portugal"},{"name":"FEUP \u2013 Faculdade de Engenharia da Universidade do Porto  Porto 4200\u2010135 Portugal"}]},{"given":"Xiaoyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Imperial College London  Exhibition Rd London SW7 2AZ UK"},{"name":"Institute of Biomedical Engineering Imperial College London  Exhibition Rd London SW7 2AZ UK"}]},{"given":"S\u00edlvia J.","family":"Bidarra","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto  Rua Alfredo Allen 208 Porto 4200\u2010135 Portugal"},{"name":"INEB \u2013 Instituto de Engenharia Biom\u00e9dica Universidade do Porto  Porto 4200\u2010135 Portugal"}]},{"given":"Diana S.","family":"Nascimento","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto  Rua Alfredo Allen 208 Porto 4200\u2010135 Portugal"},{"name":"INEB \u2013 Instituto de Engenharia Biom\u00e9dica Universidade do Porto  Porto 4200\u2010135 Portugal"},{"name":"ICBAS \u2013 Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar Universidade do Porto  Porto 4200\u2010135 Portugal"}]},{"given":"Vernon","family":"LaLone","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Imperial College London  Exhibition Rd London SW7 2AZ UK"},{"name":"Institute of Biomedical Engineering Imperial College London  Exhibition Rd London SW7 2AZ UK"},{"name":"Department of Materials Imperial College London  Exhibition Rd London SW7 2AZ UK"}]},{"given":"Bianca N.","family":"Louren\u00e7o","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto  Rua Alfredo Allen 208 Porto 4200\u2010135 Portugal"},{"name":"INEB \u2013 Instituto de Engenharia Biom\u00e9dica Universidade do Porto  Porto 4200\u2010135 Portugal"},{"name":"FEUP \u2013 Faculdade de Engenharia da Universidade do Porto  Porto 4200\u2010135 Portugal"}]},{"given":"Joana","family":"Paredes","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto  Rua Alfredo Allen 208 Porto 4200\u2010135 Portugal"},{"name":"FMUP \u2013 Faculdade de Medicina da Universidade do Porto  Porto 4200\u2010319 Portugal"},{"name":"IPATIMUP \u2013 Instituto de Patologia e Imunologia Molecular da Universidade do Porto  Porto 4200\u2010135 Portugal"}]},{"given":"Molly M.","family":"Stevens","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Imperial College London  Exhibition Rd London SW7 2AZ UK"},{"name":"Institute of Biomedical Engineering Imperial College London  Exhibition Rd London SW7 2AZ UK"},{"name":"Department of Materials Imperial College London  Exhibition Rd London SW7 2AZ UK"}]},{"given":"C. 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