Abstract
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 role of Epithelial to mesenchymal transition (EMT), Circulating Tumor Cells (CTC) and Cancer Stem Cells (CSC) has been well established in metastatic spread of disease. Activation of EMT in primary tumors generates highly invasive and migratory mesenchymal cells, which could enter in blood or lymphatic circulation. These CTCs may have CSC like properties; extends to secondary sites giving rise to metastasis.
In this thesis we have described a possible enrichment of CSC properties measured by SOX2 and CD44 as disease progressed from sensitive to refractory to therapy using three cell line panel previously derived from one SCLC patient. This thesis also includes a multicenteric clinical study where we showed that CTC’s have prognostic and predictive value in SCLC. Further we used the biopsy material from same patients and showed that tumors with high epithelial characteristics have worse overall survival. In NSCLC A549-EMT model we demonstrated that mesenchymal cells display enhanced chemoresistance, migration potential, invasion capacity and CSC properties compared to epithelial cells. We investigated the potential of CSC enrichment of esophageal adenocarcinoma (EAC) cells in 3D spheroid cell culture and subcutaneous animal model. This thesis also discussed on current and novel methods of targeting apoptosis pathways in lung cancer as therapeutic strategies.
In this thesis we have described a possible enrichment of CSC properties measured by SOX2 and CD44 as disease progressed from sensitive to refractory to therapy using three cell line panel previously derived from one SCLC patient. This thesis also includes a multicenteric clinical study where we showed that CTC’s have prognostic and predictive value in SCLC. Further we used the biopsy material from same patients and showed that tumors with high epithelial characteristics have worse overall survival. In NSCLC A549-EMT model we demonstrated that mesenchymal cells display enhanced chemoresistance, migration potential, invasion capacity and CSC properties compared to epithelial cells. We investigated the potential of CSC enrichment of esophageal adenocarcinoma (EAC) cells in 3D spheroid cell culture and subcutaneous animal model. This thesis also discussed on current and novel methods of targeting apoptosis pathways in lung cancer as therapeutic strategies.
| Original language | English |
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| Qualification | Doctor of Philosophy |
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| Award date | 16-Mar-2016 |
| Place of Publication | [Groningen] |
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| Print ISBNs | 978-90-367-8675-1 |
| Electronic ISBNs | 978-90-367-8674-4 |
| Publication status | Published - 2016 |