Heterogeneity at the invasion front of triple negative breast cancer cells
Open Access
- 1 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 10 (1), 1-9
- https://doi.org/10.1038/s41598-020-62516-8
Abstract
Identifying better predictive and prognostic biomarkers for the diagnosis and treatment of triple negative breast cancer (TNBC) is complicated by tumor heterogeneity ranging from responses to therapy, mutational burden, and clonal evolution. To overcome the gap in our understanding of tumor heterogeneity, we hypothesized that isolating and studying the gene expression profile of invasive tumor cell subpopulations would be a crucial step towards achieving this goal. In this report, we utilized a fluidic device previously reported to be capable of supporting long-term three-dimensional growth and invasion dynamics of cancer cells. Live invading and matched non-invading SUM149 inflammatory breast cancer cells were enriched using this device and these two functionally distinct subpopulations were tested for differences in gene expression using a gene expression microarray. 305 target genes were identified to have altered expression in the invading cells compared to the non-invading tumoroid cells. Gene ontology analysis of the gene panel identified multiple biological roles ranging from extracellular matrix reorganization to modulation of the immune response and Rho signaling. Interestingly, the genes associated with the invasion front differ between different samples, consistent with inter- and intra-tumor heterogeneity. This work suggests the impact of heterogeneity in biomarker discovery should be considered as cancer therapy increasingly heads towards a personalized approach.Funding Information
- Breast Cancer Research Foundation
- METAvivor
This publication has 28 references indexed in Scilit:
- Single-Cell Genetic Analysis of Ductal Carcinoma in Situ and Invasive Breast Cancer Reveals Enormous Tumor Heterogeneity yet Conserved Genomic Imbalances and Gain of MYC during ProgressionThe American Journal of Pathology, 2012
- Modulation of Invasive Phenotype by Interstitial Pressure-Driven Convection in Aggregates of Human Breast Cancer CellsPLOS ONE, 2012
- RhoC Impacts the Metastatic Potential and Abundance of Breast Cancer Stem CellsPLOS ONE, 2012
- A novel signaling pathway impact analysisBioinformatics, 2008
- Determinants of RNA Quality from FFPE SamplesPLOS ONE, 2007
- A systems biology approach for pathway level analysisGenome Research, 2007
- A collection of breast cancer cell lines for the study of functionally distinct cancer subtypesCancer Cell, 2006
- The Role of the AP-1 Transcription Factors c-Fos, FosB, Fra-1 and Fra-2 in the Invasion Process of Mammary CarcinomasBreast Cancer Research and Treatment, 2004
- The KEGG DatabasePublished by Wiley ,2002
- N-Cadherin Promotes Adhesion Between Invasive Breast Cancer Cells and the StromaCell Adhesion and Communication, 1997