Cellular map of breast tumors created in the United Kingdom
Researchers from the MRC Laboratory of Medical Sciences, Imperial College London and the UCL Genetics Institute in the United Kingdom have created a detailed cellular map of breast tumors. It revealed distinct areas with actively dividing cancer cells and clusters of cells in a dormant state. ScienceDaily reports on the results of the study, published in the journal Genome Medicine.
Cells in a dormant state
Such cancer cells do not divide actively, so chemotherapy, which mainly acts on rapidly multiplying cells, may be less effective against them. According to the study's co-lead, Alexis Barr, head of the LMS Cell Cycle Control group, these cells can evade chemotherapy, remain inactive in the tumor and later reactivate and resume proliferation.
The scientists used open data and combined single-cell RNA sequencing with spatial transcriptomics. This made it possible to determine which genes individual cells use, as well as establish their location and neighboring cell types. In tumors before treatment began, the researchers identified cells similar to therapy-resistant ones. This pattern was observed both in aggressive forms of breast cancer and in forms that develop more slowly.
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Possible protective barrier
Cells in a dormant state were often located near CXCL10-positive macrophages and myofibroblastic cancer-associated fibroblasts. The authors suggest that these immune and support cells may form a physical or biological barrier that makes it more difficult for immune cells or treatment to reach inactive cancer cells.
At the same time, the direction of the causal relationship has not yet been established. The researchers do not know whether the environment puts cancer cells into a dormant state or whether the cancer cells themselves recruit or alter neighboring cells. Increased activity of the complement system was also found in niches of dormant cells.
The authors note that the ideas generated during the analysis still require experimental verification. In their view, different areas of a single tumor may respond differently to treatment, and future therapy combinations could potentially take into account both actively proliferating and inactive cancer cells and their microenvironment.
