ICOR 2018

Marina De Rosa

Marina De Rosa, Speaker at Cancer Conference
University of Naples Federico II, Italy
Title : Characterization of tumorspheres generated from primary mesenchymal colon cancer cells for the study of colorectal cancer progression

Abstract:

EMT and its reverting process mesenchymal-epithelial transition (MET), are physiological processes occurring during embryonic development and tissue remodelling that confer plasticity to cancer cells. It has been suggested that EMT and cell plasticity could be responsible for the acquisition of chemotherapy resistance and metastasis development in several tumours, including CRCs. We previously isolated and characterized at a molecular level two primary CRC cell coltures from tumour tissues of patients 88 and 93 of our bio-bank (the T88 and T93 coltures). As previously described, T93 cells showed a CIN phenotype, while T88 cells showed a MIN one, with high MSI. We demonstrated that T88 and T93 cells were mesenchymal colon cancer cells that had undergone EMT from epithelial adenocarcinoma cells and simultaneously expressed epithelial (Cks and E-Cadherin) and mesenchymal (Vimentin and N-Cadherin) markers. High levels of EMT-associated transcription factors (Twist and Snail) and several stemness markers were also found. These finding were in accordance with previous data indicating that EMT induces the expression of stem cell-specific genes, and might represent a source of cancer stem-like cells. We also showed that incubation with LiCl, a specific GSK-3β inhibitor, induces MET. We also characterised our experimental system of adherent primary mesenchymal colon cancer cells and their paired tumourspheres more in depth, by analysing the localisation and expression of a larger panel of markers, including E- and N-cadherin, CD133, CD144v6, ALDH1 and LGR5. Furthermore, we explored the effects of LiCl on cell motility and cell plasticity of CRC cell coltures. Thus, we confirmed the epithelial/mesenchymal features of these cells and demonstrated that they were characterized by nuclear localisation of several stemness markers, including Nanog, Oct4, Sox2, LGR5, ALDH1, CD133 and CD44v6. Interestingly, we observed atypical nuclear N-cadherin, CD133 and Cd44v6 localisation in mesenchymal CRC cells. We studied the effects of LiCl, a specific GSK-3β inhibitor, on our cellular model, demonstrating that LiCl blocks the migration of T88 and T93 cells. We also observed that LiCl affects stemness features, abolishing expression of all mesenchymal and stemness markers, thus altering the dynamics of tumourspheres formation and cell plasticity. As recently demonstrated for other cancer types, such as glioma, LiCl, a drug already used in clinical practices for treating bipolar disorders, could represent an alternative therapy in colon cancer care and/or able to sensitize cancer cells to chemo-radio-therapy, through down-regulation of EMT and stem cell biomarkers, thus inhibiting crucial cancer cell features, such as motility and plasticity

Biography:

Dr Marina De Rosa achieved, with full marks, a degree in Biological Sciences at University of Naples “Federico II” in 1991. In 1998 she received the title of PhD in Biotechnology and in 2000 she received the title of specialist in Biochemistry and Clinical Chemistry. That same year, she was appointed of a four-year post-doctoral research grants. Currently she is Researcher and Assistant Professor of “Biochemistry” at the University of Naples Federico II. She is author of about 90 publications, 35 of which are articles on indexed scientific journals with a total of 496 citations (h-index:12), according to Scopus database.

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