New single-cell lineage tracing technique offers detailed insights into drivers of metastasis

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A new method for tracing real-time cancer progression across thousands of cells reveals novel insights into the rates, routes and drivers of cancer metastasis. “Our work establishes that it is now possible to uniquely distinguish tens of thousands of cells over several months of growth in vivo, reconstruct deeply resolved and accurate cell phylogenies and then interpret them to identify rare, transient events in the cells’ ancestry revealing otherwise unapparent distinction in cellular phenotypes,” write Jeffery Quinn colleagues. Metastasis is a particularly critical step in cancer progression and is predominantly responsible for cancer-related morality. However, because they are rare, transient and randomly determined, monitoring metastatic events in real time remains challenging. Quinn et al. present a novel Cas9-based, single-cell lineage tracing technique, combined with single-cell RNA sequencing, to study the progression of metastasis in a xenograft mouse model of lung cancer. The approach allowed the authors to generate phylogenies and follow the movement of tens of thousands of metastatic human cancer cells over several months of growth and dissemination. Quinn et al. found that metastases spread rapidly and dynamically, and that cancer cells from the same cell line exhibit diverse metastatic phenotypes, ranging from cancer cell populations that are incapable of metastasis to highly aggressive populations that metastasize frequently. What’s more, the authors identified distinct gene expression profiles associated with metastatic phenotypes, which revealed candidate genes with previously unknown roles in cancer progression. According to the authors, the new lineage tracing technique could inform many other difficult-to-observe facets of cellular cancer biology, including genetic mutations, microenvironment adaptation and the acquisition of resistance to therapeutic agents.

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