Intratumoral heterogeneity in a p53 null mouse model of human breast cancer

• Published in: Cancer discovery Vol. 5; no. 5; pp. 520 - 533
• Main Authors: Zhang, Mei, Tsimelzon, Anna, Chang, Chi-Hsuan, Fan, Cheng, Wolff, Andrew, Perou, Charles M., Hilsenbeck, Susan G., Rosen, Jeffrey M.
• Format: Journal Article
• Language: English
• Published: 03.03.2015
• ISSN: 2159-8274; 2159-8290
• DOI: 10.1158/2159-8290.CD-14-1101

Intratumoral heterogeneity correlates with clinical outcome and reflects the cellular complexity and dynamics within a tumor. Such heterogeneity is thought to contribute to radio- and chemoresistance since many treatments may only target certain tumor cell subpopulations. A better understanding of the functional interactions between various subpopulations of cells, therefore, may help in the development of effective cancer treatments. We identified a unique subpopulation of tumor cells expressing mesenchymal-like markers in a p53 null mouse model of basal-like breast cancer using fluorescence-activated cell sorting and microarray analysis. Both in vitro and in vivo experiments revealed the existence of crosstalk between these “mesenchymal-like” cells and tumor-initiating cells. Knockdown of genes encoding ligands upregulated in the mesenchymal cells and their corresponding receptors in the tumor-initiating cells resulted in reduced tumorigenicity and increased tumor latency. These studies illustrate the non-cell autonomous properties and importance of cooperativity between tumor subpopulations.