Year: 2015
Type: article
Abstract: UNLABELLED: 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 because many treatments may target only 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 Trp53-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 cross-talk 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. SIGNIFICANCE: Intratumoral heterogeneity has been considered one important factor in assessing a patient's initial response to treatment and selecting drug regimens to effectively increase tumor response rate. Elucidating the functional interactions between various subpopulations of tumor cells will help provide important new insights in understanding treatment response and tumor progression.
Source: Cancer Discovery
Authors: Mei Zhang, Anna Tsimelzon, Chi-Hsuan Chang, Cheng Fan, Andrew Wolff, Charles M. Perou, Susan G. Hilsenbeck, Jeffrey M. Rosen
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Breast Cancer Research Foundation, University of Pittsburgh, Dan L. Duncan Cancer Center, Baylor College of Medicine, Magee-Womens Research Institute, National Institutes of Health, Cancer Institute, University of Pittsburgh, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources
Awards: G1081826082, G1147702603, G1569999668, G1600738182, G1807857831, G2458094374, G2630554310, G2724397071, G4596676638, G4704368215, G5465708471, Center for Systematic Modeling of Cancer Development, Hormonal Regulation of Breast Cancer, G741073515, G863484009, Baylor College of Medicine Cancer Center - Cancer Center Support Grant, G99424851
OpenAlex ID: W2128527767