AbstractCancer is a leading cause of death worldwide and the number of deaths due to this disease is increasing from year to year. Unfortunately, lung cancer has the highest mortality rate among all types of cancers, in Belgium or worldwide. Thus, it is essential to improve treatments already in use and to develop new modalities to fight cancer. Radiotherapy plays an important role in cancer treatment since about 50% of all cancer patients will undergo at least one radiotherapeutic session during their illness. Any improvement in radiotherapy may therefore be of benefit for a large number of patients. One way to improve radiotherapy is to maximize the dose delivered to the tumour while minimizing damages to healthy tissues. Hadrontherapy has the advantage to spare normal tissues surrounding the tumour because of the particular ballistic of charged particles, which is characterized by the Bragg peak. Indeed, charged particles release most of their energy at the end of their track in the matter whereas the energy deposition of photons (X-rays) is intense at the entrance in the tissues and decreases exponentially with depth. Another way to improve radiotherapy is to limit tumour radioresistance by increasing our knowledge of the radioresistance mechanisms in order to disrupt them. It has been demonstrated that tumour cells are able to protect tumour associated endothelial cells by secreting growth factors which inhibit endothelial cell apoptosis and promote angiogenesis. A reciprocal dialogue seems also to occur. Consequently, the therapeutic effect of ionizing radiations is limited. In the first part of this work, we compared the effects of X-ray and alpha particle irradiations on tumour cells, derived from a lung cancer, and endothelial cells. We demonstrated that alpha particles were more effective that X-rays and that mitotic catastrophe was the main type of cell death induced by both types of irradiation. We also demonstrated that X-ray and alpha particle irradiations induced the overexpression of genes implicated in cell death, angiogenesis and inflammation. In the second part of this work, we set up a co-culture system in order to study the interplay between tumour cells and endothelial cells after alpha particle irradiation. Lastly, we performed a gene expression study of proteins, cytokines and growth factors that could play a role in tumour radioresistance. We also observed gene expression changes for proteins that could be implicated in a crosstalk between the two cell types that could activate radioresistant or radiosensitive pathways. The study of the interplay between tumour cells and endothelial cells suggests the existence of an active communication between both cell types after irradiation that could be implicated in radioresistance mechanisms. The identification of molecules involved in these radioresistance processes could lead, in a near future, to the development of new targeted drugs which will block these radioprotective signals in order to improve radiotherapy effectiveness.
|Date of Award||28 Jan 2012|
|Supervisor||Carine MICHIELS (Supervisor), Stephane Lucas (Jury), Jean-Michel DOGNE (Jury), Patricia Renard (President), Olivier Féron (Jury) & François PARIS (Jury)|
Étude des effets de radiations par rayons X ou par particules alpha sur les interactions entre cellules tumorales et cellules endothéliales
Riquier, H. (Author). 28 Jan 2012
Student thesis: Doc types › Doctor of Sciences