Breast Tumor Heterogeneity: Source of Fitness, Hurdle for Therapy Shany Koren, Mohamed Bentires-Alj  Molecular Cell  Volume 60, Issue 4, Pages 537-546 (November 2015) DOI: 10.1016/j.molcel.2015.10.031 Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 1 Model of Mammary Cell Hierarchy During embryonic development, MaSCs contribute to the luminal and basal lineages. Currently, the existence of adult multipotent MaSCs is under debate. Self-sustained unipotent luminal and basal stem cells as well as multipotent stem cells may maintain the homeostasis of the adult virgin mammary gland. The organization of their hierarchy is unknown. Molecular Cell 2015 60, 537-546DOI: (10.1016/j.molcel.2015.10.031) Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 2 Sources of Breast Cancer Heterogeneity Schematic illustration of possible sources of heterogeneity. (A) Combination of the differentiation state of the cell-of-origin and the tumor-initiating genomic alteration ([A] or [B]) is a determinant of the tumor phenotype. (B) Cell plasticity contributes to the phenotypic diversity of breast cancer. Dynamic bidirectional cell conversions occur between CSCs and non-cancer stem cells within a tumor. (C) Tumorigenesis is a multi-step branched evolutionary process. Phylogenetic lineages of clones form by genomic alteration and Darwinian selection. This genomic heterogeneity translates into phenotypic tumor heterogeneity. (D) Interaction and cross-talk between tumor cells and their microenvironment impact tumor diversity. Molecular Cell 2015 60, 537-546DOI: (10.1016/j.molcel.2015.10.031) Copyright © 2015 Elsevier Inc. Terms and Conditions