Cancer stem cells and epithelial to mesenchymal transition in lung cancer
| PhD ceremony: | Mr M.M. (Milind) Pore |
| When: | March 16, 2016 |
| Start: | 14:30 |
| Supervisor: | prof. dr. F.A.E. (Frank ) Kruyt |
| Co-supervisors: | dr. T.J.N. Hiltermann, dr. J. Meijer |
| Where: | Academy building RUG / Student Information & Administration |
| Faculty: | Medical Sciences / UMCG |
Lung cancer is a devastating disease and the number of deaths by lung cancer alone exceeds that of all other types of cancer-related deaths combined. In recent years the roles of Epithelial to Mesenchymal transition (EMT), Circulating Tumour Cells (CTC) and Cancer Stem Cells (CSC), have been well established in metastatic spread of the disease. Activation of EMT in primary tumours generates highly invasive and migratory mesenchymal cells, which could enter in blood or lymphatic circulation. These CTCs may have CSC like properties; this extends to secondary sites giving rise to metastasis.
In this thesis we describe a possible enrichment of CSC properties measured by SOX2 and CD44, as disease progressed from sensitive to refractory to therapy using three cell line panels previously derived from one SCLC patient. This thesis also includes a multicentre clinical study where we showed that CTC’s have prognostic and predictive value in SCLC. Furthermore we used biopsy material from patients and showed that tumours with high epithelial characteristics have worse overall survival. In the NSCLC A549-EMT model we demonstrated that mesenchymal cells display enhanced chemo resistance, migration potential, invasion capacity and CSC properties compared to epithelial cells. We investigated the potential of CSC enrichment of esophageal adenocarcinoma (EAC) cells in a 3D spheroid cell culture and subcutaneous animal model. We also discuss current and novel methods of targeting apoptosis pathways in lung cancer as therapeutic strategies.