American Association for Cancer Research
Browse
21598290cd141101-sup-138014_2_supp_0_nklr81.pdf (147.14 kB)

Supplementary Methods, Figure Legends, Tables S1, S3 - S6 from Intratumoral Heterogeneity in a Trp53-Null Mouse Model of Human Breast Cancer

Download (147.14 kB)
journal contribution
posted on 2023-04-03, 20:41 authored by Mei Zhang, Anna Tsimelzon, Chi-Hsuan Chang, Cheng Fan, Andrew Wolff, Charles M. Perou, Susan G. Hilsenbeck, Jeffrey M. Rosen

Supplementary Table S1. Partial list of probes preferentially expressed in the Lin-CD29HCD24L cells. Supplementary Table S3. Co-transplantation of increasing numbers of niche cells resulted in increasing numbers of tumors. Supplementary Table S4. a. Pairwise comparisons using fixed number of niche cells displayed a reduced tumor latency with increasing numbers of TICs. b. Pairwise comparisons using 10 TICs demonstrated that tumor formation was more rapid with 10 niche cells as compared to 0. c. Pairwise comparisons using 20 TICs demonstrated that tumor formation was faster with 10 niche cells as compared to 0. Supplementary Table S5. Different types of niche cells were associated with different tumor forming frequencies. Supplementary Table S6. a. No difference observed between shRNA groups for 0 niche cell relative to the control shRNA. b. No difference observed between shRNA groups for 2 niche cells relative to the control shRNA. c. A marginal difference for 10 niche cells relative to the control shRNA. d. A significant difference for 20 niche cells as relative to the control shRNA.

History

ARTICLE ABSTRACT

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. Cancer Discov; 5(5); 520–33. ©2015 AACR.See related commentary by Brooks and Wicha, p. 469This article is highlighted in the In This Issue feature, p. 453