After years of research, the team led by Prof. Zheng Zhengjun, the First People's Hospital of Shanghai Jiao Tong University, has achieved breakthroughs in the study of tumor metastasis mechanisms. They found that tumor cells can accumulate macrophages through exosomes carrying signaling molecules, escape immune surveillance, and achieve distant metastases. The relevant research papers were published in the latest issue of the international authoritative oncology magazine Cancer Research. Pancreatic cancer-based gastrointestinal cancers account for about half of the total malignant tumors. Pancreatic cancer is a kind of malignant tumor of the digestive tract, which is characterized by occult onset, rapid progress, and poor prognosis. The main reason is that it is difficult to diagnose and metastasize in the early stage. It is of great significance to elucidate the specific mechanisms of relapse and metastasis and find new targets for molecular diagnosis and treatment. The research team first used electron microscopy and NTA techniques to determine that hypoxia can increase the exocrine secretion of tumor cells. Exosomes are membranous vesicles with a diameter of 30 nm to 150 nm produced by cells in the process of endocytosis. They can carry various biologically active molecules such as DNA and miRNA, and exchange information between cells. They are widely found in blood and urine. In various body fluids such as liquids. This provides "communication means" for tumor cells to "pull gangs" to achieve "position shift." After co-incubation of exosomes secreted by tumor cells with hypoxia and macrophages, the team found that the macrophages after exocytosis were “muted†and that macrophages were “domesticated†into M2 macrophages. . Studies have shown that M2 macrophages can participate in anti-inflammatory reactions, angiogenesis, and promote tumor growth and metastasis. This shows that in the process of tumor metastasis, tumor cells can effectively use other stromal cells in the tumor microenvironment and “pull the gangs†to achieve their goals. The team used miRNA microarray technology to detect the expression of miRNA-301a under hypoxia. After co-incubation of exosomes enriched with miRNA-301a with macrophages, expression of miRNA-301a in macrophages was also observed. Obviously increased. Further research found that miRNA-301a down-regulates the PTEN tumor suppressor gene and activates PI3Kγ, the key signal molecule for M2 polarization of macrophages, thereby achieving the goal of "domesticating" macrophages. The research team examined the expression of miRNA-301a in blood exosomes of tumor patients and found that it was positively correlated with the patient's TNM staging and negatively correlated with survival. Subsequently, independent regression analysis revealed that miRNA-301a may serve as an independent prognostic factor for pancreatic cancer. In addition, a model of lung metastasis in nude mice was established by tail vein injection. It was found that macrophages induced by exosomes of tumor cells in vivo can also promote the metastasis of tumor cells. The research team for the first time confirmed the regulation of Exosomal-miR-301a in tumor immune escape and metastasis. Exosomal-miR-301a, as a cancer-promoting molecule, may become a new target for the diagnosis and treatment of pancreatic cancer-based gastrointestinal cancer, and has important theoretical and clinical significance. (Specialist reporter Yang Jing) Puyang Linshi Medical Supplies Co., Ltd. , https://www.linshihealths.com