Académie royale de Médecine de Belgique


Résumé de Cédric Blanpain


(Ont pris part à la discussion : les Prs J.-M. Foidart, N. Clumeck, Mme I. Salmon, et J.-J. Vanderhaeghen).


par Cédric BLANPAIN (ULB), invité.              

Different theories have been proposed to explain tumour heterogeneity including the cancer cell of origin. Here, we developed genetically engineered mouse models allowing lineage tracing together with oncogenic activation in different cell lineages, and assessed whether the cancer cell of origin controls tumour heterogeneity. Mouse skin squamous cell carcinoma (SCC) arising from the interfollicular epidermis (IFE) are all well-differentiated SCCs. In contrast, tumours that arise from the same oncogenic hits in the hair follicle (HF) lineages displayed considerable heterogeneity ranging from well-differentiated SCCs to fibroblastic-like cancers exhibiting epithelial to mesenchymal transition (EMT) features. I will discuss further evidence that the cancer cell of origin controls EMT-related tumour heterogeneity and the underlying molecular mechanisms that promote multilineage differentiation, tumour propagation, EMT and metastasis in primary skin SCCs. Breast cancer is the most frequent cancer in women and consists of heterogeneous types of tumors that are classified into different histological and molecular subtypes. PIK3CA and p53 are the two most frequently mutated genes and are associated with different types of human breast cancers. I will present new results uncovering the cellular origin of PIK3CA and p53 induced mammary tumors and show that the cancer cell of origin controls tumor heterogeneity. These results have important implications for our understanding of the mechanisms controlling tumor heterogeneity and the development of new strategies to block tumor initiation.