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During carcinogenesis, for example, hyaluronan (HA) homeostasis is dysregulated by cancer cells and the altered synthesis and degradation processes result in the formation of HA gradients within the tumor microenvironment. Herein, a platform is developed to study the biological role of HA gradient in breast cancer cells. Cells with different aggressiveness and expression of CD44\u2014the main HA receptor usually overexpressed in breast cancers, are selected for this study. The developed platform is compatible with several imaging modalities and allows assessment of cell density, morphology, CD44 expression, and cell motility in a function of HA density. Using high\u2010throughput analysis, it is shown that cells that do not express CD44 do not change along the gradient, while CD44 positive cells respond differently to the HA gradient depending on the level of CD44 expression and HA density. This different response is associated with the activation of different signaling pathways by the CD44\u2013HA interactions.<\/jats:p>","DOI":"10.1002\/adhm.202101309","type":"journal-article","created":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T09:05:10Z","timestamp":1635152710000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Influence of Hyaluronan Density on the Behavior of Breast Cancer Cells with Different CD44 Expression"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3085-7796","authenticated-orcid":false,"given":"Ana M.","family":"Carvalho","sequence":"first","affiliation":[{"name":"3B's Research Group \u2010 Biomaterials Biodegradable and Biomimetics Avepark \u2010 Parque de Ci\u00eancia e Tecnologia Zona Industrial da Gandra  Barco 4805\u2010017 Portugal"},{"name":"ICVS\/3B's \u2010 PT Government Associate Laboratory University of Minho  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