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Nature: Demystifying the “dormancy” mechanism of tumor cells and effectively preventing metastatic cancer
“Dormancy” mechanism of tumor cells and preventing metastatic cancer. Cancer, a life-threatening killer that threatens human health, has always been an important area that scientists are committed to solving.
Suffering from cancer is already a huge pressure for patients, and the metastasis and spread of cancer cells even makes them lose a glimmer of hope. In many cancer patients, after the primary tumor is removed, some of the tumor cells will survive the treatment and escape to other organs, leading to cancer recurrence. T
hese escaped tumor cells will stay dormant for a long time and are difficult to detect, thus greatly reducing the effectiveness of cancer treatment.
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.
The article pointed 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 cells.
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.
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. A
t the same time, in the tumor dormant environment, natural killer cells were the only immune cells with increased numbers. In contrast, there are much fewer natural killer cells in the metastatic environment of tumors, replaced by bone marrow-derived subgroups.
Therefore, the researchers inferred that natural killer cells determine the state of tumor cells. When their number increases, they will maintain the dormant state of tumor cells and inhibit their activation.
Test process and grouping
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. Factors (TNF) and interferon-γ (IFN-γ), these two types play an important role in activating natural killer cells and inducing tumor cell growth arrest. Further experiments have confirmed that natural killer cells can induce tumor cells to stay in a dormant state through interferon-γ, thereby causing tumor cells to enter dormancy.
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. A special transcription factor encoding activated hepatic stellate cells (aHSCs) markers appeared in the stroma of the tumor metastasis group, and activated hepatic stellate cells were the main driving factor of muscle fibrosis. This phenomenon It usually occurs before the onset of cancer. After comparing the data with the tumor-free cell group, the results showed that the surge of activated hepatic stellate cells would hinder the proliferation of natural killer cells, thereby activating tumor cells from a dormant state.
Activating hepatic stellate cells can do this, which is related to CXCL12, a chemokine behind it. CXCL12 can transfer tumor cells to easily metastatic tissues through its receptor CXCR4. At the same time, researchers speculate that it may be able to inhibit the active state of natural killer cells in the liver and hinder their proliferation. The experiment also verified this inference, CXCL12 will not be inhibited by natural killer cells, but will limit the proliferation of blood-derived natural killer cells isolated from breast cancer patients with liver metastases.
Throughout the trial process, the researchers also studied the treatment of cancer cell metastasis, including interleukin-15 (IL-15). 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.
This study shows that the prevention of cancer metastasis by increasing the number of natural killer cells, using interferon-γ or inhibiting the effect of hepatic stellate cells on natural killer cells will become a means worth studying. It is hoped that this method can be applied in the future and bring more hope to cancer patients.
(source:internet, reference only)