Doxorubicin-sensitive and -resistant colorectal cancer spheroid models: assessing tumor microenvironment features for therapeutic modulation

• DOI: 10.3389/fcell.2023.1310397
• Publication Date: 2023-12-22T04:22:15Z
• Authors: Ruben Valente; Sandra Cordeiro; André Luz; Maria C. Melo; Catarina Roma Rod...; Pedro V. Baptista; Alexandra R. Fern...
• Keywords: Spheroid; Viability assay; Tumor progression

Introduction: The research on tumor microenvironment (TME) has recently been gaining attention due to its important role in growth, progression, and response therapy. Because of this, the development three-dimensional cancer models that mimic interactions TME structure complexity is great relevance drug development. Methods: This study aimed characterize colorectal spheroids overtime assess how susceptibility or resistance doxorubicin (Dox) inclusion fibroblasts heterotypic influence modulate their secretory activity, namely release extracellular vesicles (EVs), Dox-mediated chemotherapy. Different characteristics were assessed over time, spheroid viability, presence hypoxia, expression hypoxia inflammation-associated genes proteins. Due importance EVs biomarker discovery with impact early diagnostics, prognostics treatment, proteomic profiling released by different 3D was also assessed. Response treatment monitored assessing Dox internalization effects structures cell viability. Results Discussion: results show distinct features are affected both fibroblasts. Fibroblasts can stabilize models, through modulation inflammation levels, as well expressions associated transcripts/proteins, promotes alterations protein profile exhibit EVs. Summarily, increase cell-cell cell-extracellular matrix interactions, making a model understand chemotherapies resistance. induction shown Dox, especially homotypic spheroids, it viability consequently chemoresistance those when exposed Dox. Taken together these highlight finding characterizing resembling more closely vivo tumors modulating