Nature Reveals the "Dormancy" Mechanism of Tumor Cells Effectively Prevents Metastatic Cancer

Cancer, a life-threatening killer that threatens human health, has always been an important area that scientists are committed to solving
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Suffering from cancer is already a huge pressure for patients, and the metastasis and spread of cancer cells makes them lose a glimmer of hope

Recently, a research team from the University of Basel in Switzerland published an article titled Hepatic stellate cells suppress NK cell-sustained breast cancer dormancy in Nature.
They used a breast cancer liver metastasis model to test on mice, thus revealing that tumor cells are dormant.
Mechanism and provide a new solution for preventing cancer cell metastasis
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The article points out that tumor dormancy is closely related to natural killer cells (NK cells) and hepatic stellate cells (HSCs), and these two types of cells play an important role in the process of tumor cell metastasis
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In this experiment, the researchers first used overall transcriptome analysis to divide the experiment into three groups: tumor cell dormancy, tumor cell metastasis, and tumor-free cells to explore the relationship between natural killer cells and tumor dormancy
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The study found that the transcriptional abundance of marker genes of natural killer cells in the tumor dormant stroma was significantly higher than that in the tumor metastasis group.

Test process and grouping

The value of natural killer cells in the three groups

So, how do natural killer cells keep tumor cells "eternally asleep"? The researchers extracted natural killer cells from the three groups of dormant, metastatic, and tumor-free cells for comparison.
The results showed that when the dormant group was compared with the metastatic group, the natural killer cells were closely related to cytokine coding pathways, including tumor necrosis.
Factor (TNF) and interferon-γ (IFN-γ), both of which play an important role in activating natural killer cells and inducing tumor cell growth arrest
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Further experiments have confirmed that natural killer cells can induce tumor cells to be in a dormant state through interferon-γ, thereby causing tumor cells to enter dormancy

Gene expression of natural killer cells in dormant and metastatic states, and the distribution of interferon-γ

In addition to studying the mechanism of tumor dormancy, the researchers also studied the process of tumor cells from dormancy to activation, and they found clues in the tumor metastasis group
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A special transcription factor encoding activated hepatic stellate cells (aHSCs) markers appeared in the interstitium of the tumor metastasis group, and activated hepatic stellate cells were the main driving factor of muscle fibrosis.

Heat map of hepatic stellate cell gene expression in dormant group and metastatic group

Activating hepatic stellate cells can do this, which is related to CXCL12, a chemokine behind it
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CXCL12 can transfer tumor cells to metastasis-prone tissues through its receptor CXCR4.

The effect of CXCL12 on the number of natural killer cells

Throughout the trial process, the researchers also studied the treatment of cancer cell metastasis, including interleukin-15 (IL-15)
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Studies have found that IL-15 can activate the proliferation of T cells and natural killer cells, stimulate the production of interferon-γ (IFN-γ), release the inhibition of CXCL12, and induce tumor cells to enter a dormant state

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Reference materials:

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