As 2D surfaces fail to resemble the tumoral milieu, current discussions are focused on which 3D cell culture strategy may better lead the cells to express in vitro most of the malignant hints described in vivo. In this study, this question is assessed by analyzing the full genetic profile of MCF7 cells cultured either as 3D spheroids-considered as “gold standard” for in vitro cancer research- or immobilized in 3D tumor-like microcapsules, by RNA-Seq and transcriptomic methods, allowing to discriminate at big-data scale, which in vitro strategy can better resemble most of the malignant features described in neoplastic diseases. The results clearly show that mechanical stress, rather than 3D morphology only, stimulates most of the biological processes involved in cancer pathogenicity, such as cytoskeletal organization, migration, and stemness. Furthermore, cells entrapped in hydrogel-based scaffolds are likely expressing other physiological hints described in malignancy, such as the upregulated expression of metalloproteinases or the resistance to anticancer drugs, among others. According to the knowledge, this study represents the first attempt to answer which 3D experimental system can better mimic the neoplastic architecture in vitro, emphasizing the relevance of confinement in cancer pathogenicity, which can be easily achieved by using hydrogel-based matrices.
Bibliografisk noteFunding Information:
M.F.C., A.V., M.K.‐F., M.M., G.L., and L.H. contributed equally to this work. The authors gratefully thank Dr. Gerhard Frank and Alexander Matthies for their support in the use of the SEM and the preparation of RNA samples. A.L.‐E. acknowledges the financial support provided by the German Research Foundation (LE 3418/2‐1). R.P acknowledges the support provided by the German Research Foundation (DFG), project number 248122450. M.F.C. thanks CONICYT for his postdoctoral fellowship. A.R.B. and A.K.B. acknowledge the financial support provided by the German Research Foundation (TRR225, A01, C03). P.C. and B.P. were supported by the Interdisciplinary Center for Clinical Research (IZKF) of the University of Erlangen‐Nuremberg. All authors thank Dr. Bernd Winkler and Prof. Georg Sauer from the Robert Bosch Hospital, for supplying the human tumor tissue and the biomedical sequencing facility (BSF) of the CeMM (Vienna, Austria) for sequencing our samples. Primary human ovarian tumor cells were isolated from patient tumor tissues, which was surgical waste from Robert Bosch Hospital, Stuttgart, Germany. The experiments were approved by the ethics committee (397/2016BO1) and all patients agreed to a formal/informed consent.
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