The National Institutes of Health first discovered that succinic acid plays a key role in tumor microenvironment.

Male-specific diseases once, how to ensure male health and ketogenic diet affect diabetes and stroke? Obese doctors sharing ketogenic literature is a big threat! Respiratory fusion virus should not come to infants under two years old to prevent postpartum urinary incontinence. Do you need the third generation urinary incontinence surgery? The biggest problem in cancer treatment is that cancer cells have the ability to destroy surrounding tissues and change the growth environment of cancer cells, so they can metastasize. For example, immune macrophages that can fight cancer cells will be transformed into tumor-related macrophages that help tumors grow because of carcinogens.

Guo, an associate researcher at the Institute of Cell and System Medicine of the National Institutes of Health, led the research team of postdoctoral researcher Wu Jingying and others. Using human cancer cell lines and tumor mouse models, they found that cancer cells will release succinic acid into tumor microenvironment. By activating succinate receptor (SUCNR 1) on cancer cell membrane, immune macrophages will be polarized into tumor-associated macrophages (TAM), thus promoting tumor growth and metastasis. The research team further cooperated with Dr. Huang Caiwang and Dr. Xu from the General Hospital of the Three Armies to test the samples of patients with non-small cell lung cancer, and found that the concentration of succinic acid in patients' blood was 65438 0.8 times higher than that of normal people, indicating that the concentration of succinic acid was highly positively correlated with tumor development. This research achievement is the first discovery in the world that blood succinic acid can be used as a biomarker for the prevention and clinical diagnosis of non-small cell lung cancer, which is expected to provide a new direction for cancer treatment in clinical strategy and new drug research and development. The research results were published in the international authoritative journal Molecular Cell in June (109).

Tumor microenvironment refers to the surrounding environment where tumor cells exist, including peripheral blood vessels and immune cells. Generally speaking, cancer cells will release soluble molecules in the tumor microenvironment, and at the same time, they will try to create an environment suitable for the growth of cancer cells by affecting the surrounding immune cells. In the tumor microenvironment, immune macrophages are the main cell group and are often targeted by cancer cells.

The research team analyzed the culture media of different cancer cell lines by comparative metabonomics, and found that cancer cells (including lung cancer, breast cancer, prostate cancer and colorectal cancer) would release succinic acid to the tumor microenvironment, and transmit signals by activating succinate receptor (SUCNR 1) and PI3K/HIF- 1 downstream, thus polarizing immune macrophages into. Dr. Guo said that the mechanism behind the elimination of cell lines by succinate receptors and animal experiments is that succinic acid promotes the polarization of immune macrophages into tumor-related macrophages by activating succinate receptors. Further analysis showed that the co-culture of cancer cells and macrophages showed that the macrophages induced by succinic acid had the ability to promote the migration of cancer cells. At the same time, in the tumor mouse model injected with succinic acid, it is also found that succinic acid can increase tumor-related macrophages in the tumor environment, and the phenomenon of cancer cell metastasis is more obvious. The above analysis results show that succinic acid plays an important role in the tumor microenvironment of cancer cell growth and metastasis.

At the same time, the research team analyzed the clinical data and compared the blood succinic acid concentration of patients with non-small cell lung cancer with that of healthy people. It is found that patients with lung cancer have high blood succinic acid concentration, and the statistical analysis method of AUROC also shows that there is a high degree of discrimination between blood succinic acid and the growth and development of lung cancer, which indicates that blood succinic acid concentration will become a biomarker for diagnosing the development of lung cancer.

Dr. Guo said that by unraveling the key mechanism of succinic acid in tumor microenvironment, it will be helpful to develop biomarker detection kits for cancer medical treatment and targeted drugs for anti-cancer monoclonal antibodies in the future. At present, the research team has developed anti-succinate monoclonal antibodies, and confirmed in tumor mice experiments that anti-succinate monoclonal antibodies can effectively inhibit the generation of tumor-related macrophages and the metastasis of cancer cells, thus improving the survival rate of tumor mice. At present, the research results of "serum succinic acid as a biomarker for cancer diagnosis and anti-succinic acid monoclonal antibody for cancer treatment" are applying for a temporary patent in the United States, which is believed to bring new directions for the development of cancer drugs and medical strategies in China in the future.

Subject: National Institutes of Health, succinic acid, cancer.