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Invasive growth of a tumour occurs within an ecosystem where a continuous communication exists between cancer cells and tumour-associated host cells. Metastatic tumours present several ecosystems: the primary tumour, the lymph node metastases and the sites of distant metastases. Those ecosystems are communicating between each other.Our project aims to apply this concept to rectal cancer treated by neoadjuvant radiochemotherapy, and to study the effect of this neoadjuvant treatment on the ecosystem.Myofibroblasts belong to the host cells group. These cells play a role in wound healing and have been implicated recently in promotion of tumour invasion and in metastatic dissemination of several cancer types.The effect of radiochemotherapy on myofibroblasts is unknown. However, patients with rectal cancer who have undergone preoperative radiotherapy and who develop local recurrence, more frequently present distant metastases than patients who did not receive this treatment. In a preliminary study, we observed that alpha-SMA (marker of myofibroblastic differentiation) expression is increased in rectal cancer and its metastatic lymph nodes as compared to cancer-free rectal and lymph node tissues. The expression was higher in irradiated than in non-irradiated tissues. Furthermore, transcriptome analysis of irradiated myofibroblasts showed an induction of genes implicated in the cell cycle such as IGF1 which is a key regulator of apoptosis.Our hypothesis is that neoadjuvant treatment in rectal cancer, more specifically radiotherapy, induces alterations in mesenchymal cells promoting tumoural recurrence and metastases. To confirm this hypothesis, we study immunohistochemical expression of several markers in two rectal cancer cohorts: irradiated and non irradiated. By in vitro cultures, we assess molecules secreted by irradiated myofibroblasts. Finally, animal models allow us to study myofibroblast implication in metastasis formation.
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