The most deadly aspect of breast cancer is metastasis. It spreads cancer cells throughout the body. Researchers have now discovered a substance that suppresses the formation of metastases. In the journal Cell, the team of molecular biologists, computational biologists, and clinicians have identified a drug that suppresses the spread of malignant cancer cells and their metastasis-seeding ability.
Circulating tumor cells (CTCs) are cancer cells that leave a primary tumor and enter the bloodstream, on their way to seeding distant metastases. These so-called CTCs can be found in the blood of patients as single cells or cell clusters. CTC clusters are the precursors of metastases. The research team has discovered that CTC cluster formation leads to key epigenetic changes that facilitate metastasis seeding.
The authors profiled DNA methylation landscape of single CTCs and CTC clusters from breast cancer patients and mouse models on a genome-wide scale. They found that binding sites for stemness- and proliferation-associated transcription factors are specifically hypomethylated in CTC clusters, including binding sites for OCT4, NANOG, SOX2, and SIN3A, paralleling embryonic stem cell biology.These changes enable CTC clusters to mimic some properties of embryonic stem cells, including their ability to proliferate while retaining tissue-forming capabilities. The scientists have also shown that these epigenetic changes are fully reversible upon the dissociation of CTC clusters.
In their search for a substance that suppresses metastasis development, the research team tested 2486 FDA-approved compounds used for a number of different indications. They found Na +/K + ATPase inhibitors with the unexpected ability to dissociate patient-derived CTC clusters. This drug-based dissociation of CTC clusters into individual cells also resulted into epigenetic remodeling and prevented the formation of new metastases.
Disrupting circulating tumor clusters prevents metastasis
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