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

• Published in: International journal of molecular sciences 2019-07, Vol.20 (14), p.3568
• Main Authors: Al Ameri, Wafa, Ahmed, Ikhlak, Al-Dasim, Fatima M, Ali Mohamoud, Yasmin, Al-Azwani, Iman K, Malek, Joel A, Karedath, Thasni
• Format: Article
• Language: English
• Subjects: 3D models; Adenosine Triphosphate - metabolism; Angiogenesis; Cell adhesion; Cell adhesion & migration; Cell culture; Cell division; Cell growth; Cell Line, Tumor; Cell Movement - drug effects; Chemoresistance; Collagen; EMT; Enzyme inhibitors; Epithelial-Mesenchymal Transition - drug effects; Extracellular Matrix; Female; Gene expression; Genes; Genotype & phenotype; Humans; Hypoxia; In vivo methods and tests; Kinases; Metastases; Metastasis; Molecular modelling; Nutrients; Organoids; Ovarian cancer; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Protein Kinase Inhibitors - pharmacology; Receptors, Transforming Growth Factor beta - metabolism; Signal Transduction - drug effects; SKOV3; Spheroids; TGF-β; Transforming Growth Factor beta - metabolism; Tumor cell lines; Tumor Cells, Cultured; Tumors; Two dimensional analysis; Two dimensional models
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20143568

Transcriptome profiling of 3D models compared to 2D models in various cancer cell lines shows differential expression of TGF-β-mediated and cell adhesion pathways. Presence of TGF-β 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-β 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-β is cell-type specific, we decided to select two promising ovarian cancer cell lines as model systems to study EMT. TGF-β 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-β can induce EMT and invasion in cancer cells by turning them into aggressive phenotypes. TGF-β receptor kinase I inhibitor (LY364947) can revert the TGF-β effect in these cells. In a nutshell, TGF-β 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-β and its inhibitor is cell-type specific and not cancer specific.