RNA-Seq of 3D printed melanoma cells in Cellink Bioink (CIB) or Matrigel

Tumor dormancy is thought to be mediated by the cellular microenvironment. However, mechanisms of inducing and revoking dormancy remain to be elucidated, in order to develop advanced therapeutic options.Here, we 3D printed melanoma cells in hydrogels as substitute of the extracellular matrix. By using Cellink Bioink (CIB) or Matrigel, we induced a quiescent and a proliferative phenotype of melanoma cell lines, respectively. RNA-Seq of these differentially cultured cells and subsequent bioinformatical analyses, reflect the quiescent cell state e.g. by revealing significant downregulation of genes associated with cell cycle progression and cellular reproduction in CIB-culture. Broad bioinformatical and additional wet chemical analyses undermine the crucial role of the ECM in the induction of the observed quiescent phenotype. Strikingly, here we identified the mechanosensory gene FHL2 as one early sensor of changes in the ECM and suggest a FHL2-p21/AP-1 axis contributing to the quiescent phenotype of melanoma cells in CIB.Our newly developed model and the respective RNA-Seq data can now be used to further elucidate the life-threatening phenomenon of cellular tumor dormancy and recurrence, with respect to the extracellular matrix and signaling pathways involved.