Zhejiang University Shen Huahao/Ying Songmin team's Science publication reveals that eosinophils promote tumor metastasis

Tumor metastasis is an important risk factor that threatens the lives of patients, and it is also one of the problems that the medical community has been striving to overcome.

Recently, the Zhejiang Provincial Key Laboratory of Respiratory Disease Diagnosis, Treatment and Research, the Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital of Zhejiang University School of Medicine, Professor Shen Huahao and Professor Ying Songmin’s team discovered that eosinophils play a behind-the-scenes role in tumor metastasis.
This research will provide potential targets for the treatment of cancer patients.

Recently, Professor Shen Huahao and Professor Ying Songmin, as co-corresponding authors, published a research paper entitled: Eosinophilic inflammation promotes CCL6-dependent metastatic tumor growth in Science Advances, a sub-Journal of Science.

The dual identity of positive vs.
negative eosinophils Eosinophils are a type of white blood cell.
Although they account for less than 5% in the blood, they have a great effect.
They not only kill bacteria and parasites, but are also allergic.
Very important effector cells in diseases such as bronchial asthma.

The team of Professor Shen Huahao and Professor Ying Songmin has been committed to the study of the pathological role and related mechanisms of eosinophils in various diseases including asthma, lung injury and tumors.

As early as 2003, they were the first to prove that eosinophils can directly cause asthma.

In subsequent studies, the research team also revealed that mature eosinophils can regulate the most upstream stem cells, and identified the key chemokine CCL6, confirming the important regulatory role of eosinophils on hematopoietic stem cells during the onset of asthma.
, It has perfected a comprehensive understanding of the function of eosinophils.

Not only that, they further confirmed the pathological role of eosinophils secreting high levels of CCL6 in asthma inflammation, and systematically studied its homologous factor CCL15/CCL23 in asthma patients, which promotes asthma by activating CCR1 receptors.
Airway inflammation.

Targeting the above-mentioned chemokines and their receptors can significantly alleviate asthma airway inflammation.
In addition to the current clinical application of targeting IL-5 and its receptors, it provides targeted blocking chemokines and their receptors for the treatment of asthma.
Experimental basis.

In other words, eosinophils do not always appear in a "positive image" in the living body, at least, in asthma, it plays a negative role.

So, what role does eosinophils play in tumor diseases? In the early 1980s, scientists had discovered the phenomenon of tumor-related tissue eosinophilia in a variety of tumors, including lung cancer, and it has a certain correlation with the patient’s prognosis, suggesting that eosinophils may be involved The occurrence and progression of tumors.

But until recent years, basic research has gradually revealed that eosinophils directly regulate tumor progression through direct interaction with tumor cells or indirectly through the tumor microenvironment.

"However, most of these studies focused on the positive significance of eosinophils in anti-tumor activities, and only a few papers put forward opposing views.

Obviously, the role of eosinophils in tumors is still controversial.

" Ying Songmin said .

So, what are the facts? The increase in eosinophils promotes the colonization and metastasis of tumor cells to the lung, which is like a magnet.
The role of eosinophils is the villain.
Tumor metastasis is where malignant tumor cells continue to grow from the primary site, through lymphatics, blood vessels, or body cavities, to other sites.
One process.

"Tumor metastasis has to face many hurdles.
To put it simply, it means being able to get out, keep it, and grow out.
Only when every step is successful can it really form a metastasis.

Among them, colonization and growth are the key link.

" Ying Songmin Said that, for this reason, the research team followed the vine and began to study the mechanism of eosinophils in the process of tumor cell colonization and growth from experiments in inflammation model mice starting in 2016.

Where is the breakthrough in this five-year study? Shen Huahao said that past research only controlled the number of eosinophils, so it was difficult to draw a clear conclusion.

"We have used advanced genetic tools to knock out some of the eosinophils of experimental mice, and find out the difference between eosinophils and tumor metastases by observing the difference between eosinophilic mice and non-eosinophilic mice.
relationship.

"team found a result, eosinophils as a magnet to attract block the migration of tumor cells, relative to normal mice, 3-5 times higher number of mice tumor metastasis inflammation.

Schematic diagram of the molecular mechanism of eosinophils promoting tumor metastasis through the CCL6-CCR1 axis.
Combined with research in related fields, Ying Songmin pointed out that the role of eosinophils in tumors is a "double-edged sword", and the role of eosinophils in anti-tumor depends on Specific stimulus conditions in the microenvironment, such as IFN-γ-activated eosinophils, can directly kill tumor cells or regulate anti-tumor immune responses to play a beneficial role.
"We should not ignore allergic airway inflammation or inactive states.
The eosinophils under the constitutive expression of key active molecules promote the adverse effects of tumor metastasis.

"Shen Huahao said that with more in-depth research and discovery of the role of eosinophils and key molecules in chronic airway inflammation and tumors, The structural characteristics of the interaction between important chemokines and receptors and the development of targeted drugs are imminent.
“Next, we will further observe and verify the experimental results in cancer patients with allergic diseases.
In addition, the team has also Breakthroughs have been made in the study of the structural characteristics of the interaction between chemokines and receptors.

"The 2017-level doctoral student Li Fei of the Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Zhejiang University School of Medicine, and the 2015-level doctoral students Du Xufei and Lan Fen Deputy Chief Physician and Deputy Chief Physician Li Na are the co-first authors of the paper.

Professor Shen Huahao is the main corresponding author, and Professor Ying Songmin is the co-corresponding author.

Link to the paper: https://advances.
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