Guohong Hu, a researcher at the Institute of Nutrition and Health, was invited to discuss the frontiers of tumor metastasis research in the journal Cancer Cell

With the diversification and precision of tumor treatment strategies, the prognosis of tumor patients has been effectively improved, but distal organ metastasis is still the most important cause of death of cancer patients, and how to inhibit and eliminate distal organ metastases has always been one of the main challenges in the field of
oncology.
In recent years, with the continuous deepening of scientists' analysis of the characteristics of tumor cells and the microenvironment of distal organ metastasis, our understanding of the mechanism of distal tumor metastasis has been deepened
.
However, many biological questions about distant metastases of tumors remain to be solved
.
Cancer Cell invited relevant experts to discuss the research progress and future development direction related to distant tumor metastasis in recent years, and published in the Voices column on August 8, 2022, discussed why tumor cells that spread to distal organs can enter a dormant state for many years, how to achieve immune escape, how to obtain tolerance to systemic treatment, and which microenvironmental components in distal organs regulate the formation of metastases
。 Hu Guohong's research group of Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences was invited to make a cutting-edge analysis on the function, research progress, opportunities and challenges of neutrophil extracellular traps (NETs) in tumor metastasis
.

NETs are extracellular DNA reticular fibers released by neutrophils that bind histone and protein particles, and the initial study showed that NETs can inhibit and kill microorganisms that invade the organism, while NETs play a more facilitating role
in tumor metastasis 。 Researcher Hu Guohong pointed out that NETs attract and capture disseminated tumor cells through their DNA, and at the same time reshape the metastatic microenvironment through various proteins they carry, promote the spread and growth of tumor cells, and basically play a role in promoting all steps of distant tumor metastasis such as migration, invasion, immune escape, spread and metastatic dormancy reactivation
.
The number of reports of NETs promoting tumor metastasis is growing rapidly, indicating the important role of NETs in the occurrence of distant tumor metastases, suggesting the potential value
of NETs as therapeutic targets for tumor distal metastases.
At present, there are still many gaps in our understanding of how tumors induce NETs and the molecular mechanisms of the process of NETs.
There are also differences in the strength of NETs in different organs where tumor metastases occur, and the mechanism behind them needs to be further studied; Whether there is a population of tumor-associated neutrophils that are more likely to develop NETs during tumor metastasis also needs to be further analyzed and explained
.
The resolution of the above problems will contribute to the development
of new strategies for tumor metastasis therapy targeting NETs.

Researcher Hu Guohong has long been concerned about the interaction
between disseminated tumor cells and the microenvironment of distal organs.
The series of works has discovered the functional mechanisms by which tumor cells interact with cells in the microenvironment of distant organs and promote metastasis during tumor metastasis (Cell Res 2012; J Clin Invest 2014; Nat Cell Biol 2017; Cancer Cell 2021,
et al.
).
。 In 2021, Hu Guohong's research team elucidated the functional role of histoproteinase C (CTSC) in promoting lung metastasis in breast cancer cells by regulating neutrophil infiltration and formation of NETs in the metastatic microenvironment, and confirmed that the application of the clinical second-stage small molecule compound AZD7986 that specifically inhibits CTSC in a mouse model of in situ spontaneous lung metastasis can significantly inhibit the occurrence of breast cancer metastasis
。 The study highlights the important role of NETs in tumor lung metastases and demonstrates the feasibility and potential clinical value of tumor metastasis therapy strategies targeting NETs (Cancer Cell 2021
).

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