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Zhang Zhigang, a researcher, and Sun Yongwei, the director of the Bile Pancreatic Surgery Department from the State Key Laboratory of Oncogenes and Related Genes of Shanghai Cancer Institute in affiliated Renji Hospitalalong with their team have recently published an article in the international famous medical journal Gastroenterology (Journal of Gastroenterology, IF = 18.187) which is entitled “Increased Serotonin Signaling Contributes to the Warburg Effect in Pancreatic Tumor Cells Under Metabolic Stress and Promotes Growth of Pancreatic Tumors in Mice”. The study illustrates the neurotransmitter serotonin (5 - HT) systemand their disturbance are involved in the microenvironment of pancreatic tumors, and proved that the 5 - HT promotes proliferation of pancreatic cancer cells under metabolic stress through regulating aerobic glycolysis, and then contributes to the progression of pancreatic cancers, which is the exact evidence of the role of neurotransmitter system in tumor regulation and further interprets the idea of systemic regulation of tumor. This is another new production after Renji hospital cooperates with Shanghai Cancer Institute.
According to Sun Yongwei, the main leader of the project: the pancreatic ductal adenocarcinoma (PDAC), one of the most malignant digestive malignant tumors, are very difficult to diagnose and treat, and has an increasing morbidity and mortality in recent years with a 5-year survival rate less than 6%, which is why it is called the king of “cancer” with worst prognosis. The most typical characteristics of PDAC is the hyperplasia of connective tissues，and in PDAC, up to 90% of tumor components can be mesenchyme, which is quite different from other tumors. To meet the increased anabolic needs for rapid division and proliferation, cancer cells require a lot of energy, which usually relies on the decomposition of glucose. Since it will lead to poor blood supply and nutrient deficiency in pancreatic tumor cells, how can they continue to make the best use of these limited energy sources in this extreme survival condition to maintain their own malignant biological function?
After more than four years of effort, Zhang Zhigangand his team have found out that it is the chaotic 5-HT system in the tumor microenvironment that influences this link. 5 - HT secreted by the tumor cells themselves will bind to HTR2B receptorsthrough autocrine, and then activate downstream signaling pathways, which will increase the aerobic glycolysis in tumor cells under metabolic stress to providemuch materials for cell growth. In addition, SB204741, a selective HTR2B antagonist, significantly inhibites the growth of pancreatic cancer cells in KPC and PDX models. Meanwhile, the HTR2B antagonists have been involved in the clinical trial of pulmonary hypertension,and may be a protential drug for the treatment for PDAC due to its good safety.
“Our study has found a magic weapon for the energy use in PDAC and has elucidated its mechanism,” Zhang said excitedly,“ What is more exciting is that its growth is significantly suppressed when we take away this energy weapon. More interestingly, drugs targeted at this magic weapon have begun clinical trials for pulmonary hypertension treatment, so wemay have revealed another potential use of this old drug for the treatment of PDAC, which will significantly shorten the time length for this drug into the clinical trials, and provide a new direction for pancreatic cancer treatment.”
The articles published in Gastroenterology will have important clinical significance, and have positive effects in the promotion of pancreatic cancer treatment and improvement of the prognosis of patients with PDAC, which will bring the Gospel to more patients in the future.
It is reported that the tumor is a kind of systemic disease characterized by multiple etiology, multi-gene participation and abnormal growth of local tissues, which is the pathological change of the body - organ - tissue. Some important regulators in the tumor microenvironment, such as glucocorticoids, catecholamine, acetylcholine, corticosteroids, immune molecules and many extracellular matrix proteins in microenvironment, will affect all aspects of tumor progression, such as pathogenesis, immune escape, invasion and metastasis, which also indicates thenetwork composed of nerve - hormones - secreted proteins plays an important role in the process of tumor progression.
According to Dai Huili, the vice President of Renji Hospital, after the merge with Shanghai Cancer Institute, with the support of GuJianren, the honorary director of Shanghai Cancer Institute, Renji Hospital has established the academician fund, which will spend 1 million yuanannually on carrying out research on the basic and clinical areas of tumor.One project will be funded every year, and must be approved by at least three academicians, which can fail must be original and exploratory. The team led byZhang Zhigang and Sun Yongwei is one of these projects, and has been committed to the impacts of nerve - endocrine - immune factors on the pathogenesis and development of tumors for four years, and finally after a series of exploration in the systemic regulation and control of tumor microenvironment, they found that a variety of neuroendocrine factors can regulate the tumor microenvironment and then affect the development and metastasis of tumor, which is one of the important achievements after this partnership between the hospital and institute.