The "safety net" of neutrophils may promote cancer cell metastasis and proliferation.

, June 23, 2020 /PRNewswireBIOON/ -- Neutrophils are a special immune cell that provides the body with the first immune defense against infection, however, in many cases, it has the ability to promote cancer metastasis, i.eto allow cancer cells to migrate from primary sites and grow in other parts of the body, according to a study published in the international journal
naturePhoto: Emma Nolan et alNature(2020) doi: 10.1038/d41586-020-01672-3
a key feature of neutrophil cells is the ability to squeeze a special structure called neutrophil extracellular trap into the surrounding environment, which is composed of A DNA network that best encases special enzymes that are toxic to microorganisms, capable of capturing and killing Invasive microorganisms, in the lungs, NETs can be induced by inflammation, and their antitumor activity is also related to NET-related enzymes, and now there is growing research evidence that NETs can mediate the occurrence and progression of cancer attacks, but researchers do not know how NETs enhance cancer metastasis, and there have been no previous studies of the molecular mechanisms that promote cancer cell perception of NETs, and researcher Yang and others have revealed that these NETs promotetumorsthe molecular mechanism formedfirst, researchers assessed the status of NETs in primary and metastatic tumors in 544breast cancerpatients, which are rare in primary tumor sites but high in the liver (a common site for breast cancer spread), and found that high levels of NET DNA in the blood of early breast cancer patients are directly related to the subsequent spread of cancer to the liver, suggesting that NET DNA in blood samples can be evaluated as a new method of pre-diagnosisTo study the association between NETs and cancer cells in the body, the researchers transferred human or mouse-derived breast cancer cells to mice and analyzed metastatic tumor cells, and found that NETs accumulatein in the liver of the mouse model tested, a finding consistent with the researchers' analysis of tumortumor
s in the body of cancer patientsresearcher Yang et alstudy mouse models found that NETs are induced in the liver before metastatic cancer cells are detected, and that the efficiency of cancer cell transfer to the liver depends on NETs, because the cancer metastasis in mice is significantly damaged after removing NETs, whether through DNA degradation enzyme DNase I or through genetic
genetic modification of mice to lack the key enzymes needed to formIn previous studies, researchers said net-dependent liver metastasis was triggered by an indirect mechanism by NETs for physical capture of cancer cells, and Yang and others found that in vitro tests, NET DNA can directly stimulate the migration and adsorption of human breast cancer cellsthen the researchers wanted to shed light on the molecular mechanisms of this migration, by tagging net DNA and using it as bait to capture and identify specific proteins that interact with it, and the researchers found a receptor called CCDC25, which can bind to NET DNA, which is present on the surface of cancer cells and binds to NET DNA with higher specificity and affinity, thus promoting the perception of NET by cancer cells, and by identifying specific parts of the DNAThe researchers confirmed that the stimulation of cell migration received by NET was driven by CCDC25, which showed that in vitro by removing human breast cancer cells or patients with primary breast cellstumortumor spout spout snrIn the study, which revealed the key role of LPS in inducing NETs-related lung metastasis, the researchers said that when mice with missing CCDC25 were used to simulate spontaneous breast cancer (MMTV-PyMT mice), there was a similar decrease in cancer cell metastasis in the lungs when LPS was treated, and it was interesting to note that the interaction between CCDC25 and NET DNA may occur in the context of infectionIts effect on liver metastasis occurs spontaneouslyresearchers reveal howtumor
cells benefit from interactions with NETs, using CCDC25 as a bait to extract proteins that interact with CCDC25 in cancer cells, so that researchers can identify a type of protein-related kinase called a blockprotein (nexus) ILK), which regulates processes such as cell migration and proliferation, when ILK is removed or its downstream signal partner, the beta-parvin protein, is inactivated, the growth and movement of in vitro cancer cells will be significantly impaired, and the metastasis of cancer cells in the mouse body to the liver will also be reducedThe results suggest that the binding between NET DNA and CCDC25 may enhance malignant cancer cell behavior by activating the ILK-mediated cascade signal responseresearcher Yang et alsaid that NET DNA's ability to promote liver cancer metastasis is not unique to breast cancer cells, and researchers in mice in colon cancer patients who metastasized and injected human colon cancer cells, had also observed NTEs if human breast and colon cancer cells could be engineered to increase CCDC25 levels It can contribute to cancer metastasis in mice given these cells, and importantly, researchers have also found a link between high levels of primary tumor and shorter patient survival, suggesting that monitoring the expression of CCDC25 may be used for cancer prevention purposes future researchers will also need to study the feasibility of targeting CCDC25's anticancer therapy, and researchers will also need to analyze the expression of CCDC25 in different cell types and their possible function in normal cells, and now researchers have identified the exact extracellular part of CCDC25's interaction with NET DNA, which may help develop special inhibitors to block the interaction between the two, or this targeted therapy may help preserve other benefits of NETs that help fight infections Compared to other metastasis sites, researchers do not yet know why NET accumulation is prone to in the liver, in the case of mammalian bowel cancer, the release of NETs in neutrophils or associated with the uplift of the complement C3a, Which is produced mainly in the liver, which can be combined with receptors on the neutrophils Before liver metastasis, the activation of the complement pathway occurred in the mammalian liver, so the researchers speculated that this might be a supplement-dependent NET-forming stimuli, but the specific mechanism researchers don't know The findings of researcher Yang et al represent a very significant advance in the field of cancer diffusion research, which could help researchers develop new strategies to inhibit the effects of NET on cancer metastasis, and the data provide a possible way for researchers to predict cancer metastasis by monitoring levels of NET DNA in the blood (BioValleyBioon.com) References: Emma Nolan and Ilaria Malanchi Neutrophil 'safety net' causes cancer cells to metastasize and proliferate , Nature (2020) doi: 10.1038/d41586-020-01672-3
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