Cell Type-Specific TGF-beta Mediated EMT in 3D and 2D Models and Its Reversal by TGF-beta Receptor Kinase Inhibitor in Ovarian Cancer Cell Lines

Transcriptome profiling of 3D models compared to 2D models in various cancer cell lines shows differential expression of TGF-beta-mediated and cell adhesion pathways. Presence of TGF-beta in these cell lines shows an increased invasion potential which is specific to cell type. In the present study, we identified exogenous addition of TGF-beta can induce Epithelial to Mesenchymal Transition (EMT) in a few cancer cell lines. RNA sequencing and real time PCR were carried out in different ovarian cancer cell lines to identify molecular profiling and metabolic profiling. Since EMT induction by TGF- beta is cell-type specific, we decided to select two promising ovarian cancer cell lines as model systems to study EMT. TGF-beta modulation in EMT and cancer invasion were successfully depicted in both 2D and 3D models of SKOV3 and CAOV3 cell lines. Functional evaluation in 3D and 2D models demonstrates that the addition of the exogenous TGF- beta can induce EMT and invasion in cancer cells by turning them into aggressive phenotypes. TGF-beta receptor kinase I inhibitor (LY364947) can revert the TGF-beta effect in these cells. In a nutshell, TGF-beta can induce EMT and migration, increase aggressiveness, increase cell survival, alter cell characteristics, remodel the Extracellular Matrix (ECM) and increase cell metabolism favorable for tumor invasion and metastasis. We concluded that transcriptomic and phenotypic effect of TGF-beta and its inhibitor is cell-type specific and not cancer specific.