The EACR’s Top 10 Cancer Research Publications is a regular summary of the most interesting and impactful recent papers in cancer research. It is curated by the Board of the European Association for Cancer Research (EACR).
The list below appears in no particular order, and the summary information has been provided by the authors.
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A.C. Rios et al., Cancer Cell 35, 618–632 April 15, 2019
“This paper was great reading. It presents a pipeline for studying breast tumor heterogeneity and plasticity using 3D models from the Visvader lab.” Therese Sørlie, EACR Board member
Cancer biology: LSR-3D imaging to unveil the clonal landscape of breast cancer in mouse models
Summary of the findings
Unraveling the inherent 3D cellular organization of biological specimens is essential for understanding developmental and disease processes, including cancer. While modern microscopy ideally requires the visualization of both fine cellular details and overall tissue architecture within a single biological sample, this remains technically very challenging. We have developed a method of sample preparation and immunofluorescent labeling that enables visualization of intact organs and importantly, tumoral tissues in 3D which enable for Large-scale, Single-cell Resolution 3D (LSR-3D) imaging. Combined with advanced multi-colored lineage tracing in mouse models of tumorigenesis, we observed that even when harboring the same cancer-driving mutations, only a few cellular clones contribute to cancer progression.
Despite this profound clonal competition and restriction, however, breast tumors remain highly heterogenous. We managed to reconcile these seemingly contrasting observations by providing proof of intraconal plasticity evolving over time during tumor development, with clonal cells displaying varying levels of EMT transition. As a result, some cells from the same clone remained epithelial, while others progressed towards mesenchymal identity. Strikingly, most clones harbored cells that had undergone EMT, suggesting both widespread clonal plasticity, as well as an important role for EMT in carcinogenesis (Cancer Cell 2019).
