DEMETTER Pieter

Units

The main research themes of the laboratory focus on the identification and validation of new biomarkers in human cancers with diagnostic, prognostic and theragnostic purposes. The research activities combine fundamental and clinical aspects. For more than 15 years, our investigations have been focused on protein biomarkers in human tissue samples, animals and in vitro models. Immunohistochemistry (IHC) plays an essential role in the validation of these biomarkers because, as opposed to other biochemical approaches, this technology enables morphological control and thus protein localization at histological and cellular levels. A close collaboration with the Laboratory of Image Synthesis and Analysis (LISA, Ecole polytechnique, U.L.B., www.lisa.ulb.ac.be) allows us to develop standardized tools for characterizing protein expression by using the multiple abilities provided by digital image analysis. From this collaboration was created the interfaculty unit, DIAPath (Digital Image Analysis in Pathology, www.ulb.ac.be/rech/inventaire/unites/ULB723.html), which is included in the Center for Microscopy and Molecular Imaging (CMMI, Biopark of Gosselies, www.cmmi.be).Our know-how in biomarkers is often requested by other university and biotech research teams. These collaborations lead us to analyse human tumours from many origins as well as pathologic tissues from other diseases, such as inflammatory diseases, graft-versus-host or diabetes.

Projetcs

Role of myofibroblasts in the recurrence of rectal cancer treated by neoadjuvant radiochemotherapy

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.