Abstract SY45-01: Defining the origin of tumor heterogeneity in epithelial cancers

Abstract

Abstract Different theories have been proposed to explain tumor 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 tumor heterogeneity. Mouse skin squamous cell carcinoma (SCC) arising from the interfollicular epidermis (IFE) are all well-differentiated SCCs. In contrast, tumors 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 tumor heterogeneity and the underlying molecular mechanisms that promote multilineage differentiation, tumor 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 mammary tumors. These results have important implications for our understanding of the mechanisms controlling tumor heterogeneity and the development of new strategies to block tumor initiation. This work is supported by the WELBIO, the FNRS, the Fondation Bettencourt-Schuler and the Fondation Baillet-Latour. Citation Format: Cedric Blanpain. Defining the origin of tumor heterogeneity in epithelial cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY45-01. doi:10.1158/1538-7445.AM2015-SY45-01