Cell Breakthrough: Revealing the biological mechanism of obesity that causes pancreatic catheter adenocarcinoma - endocrine-exocrine signal drive!

May 6, 2020 / -- A recent study led by Professor Mandar Deepak Muzumdar of the Department of Genetics and the Institute of Cancer Biology at Yale University School of Medicine showed that endocrine-exocrine signals drive obesity-related pancreatic catheter cancer (pan "Endocrine-Exocrine Signaling Drives Obesity-Associated Pancreatic Ductal Adenocarcinoma," according to research published in the journal Cell.
This study highlights the following conclusions: 1) obesity accelerates the development of carcinogenic Kras-driven pancreatic catheter tumors in mice; 2) genetic or dietary weight loss can prevent the progression of pancreatic cancer; 3) obesity is associated with abnormal expression of intestinal trypsin peptides in islet cells; and 4) expression of intestinal trypsin in islet cells promotes the development of pancreatic catheter cancer.
picture source; Cell obesity is a major and changeable risk factor for pancreatic catheter adenocarcinoma, but it is unclear how and when obesity causes PDAC to progress.
In order to uncover the secrets, Katherine Minjee Chung et al., under the leadership of Professor Muzumdar, used the self-contained mouse model to demonstrate the causal and reversible effects of obesity in early PDAC progression, suggesting that obesity significantly increased the occurrence of tumors, and that genetic or diet-induced weight loss prevented the development of cancer.
molecular analysis of human and mouse samples identified micro-environmental changes caused by obesity, which, rather than new drive gene mutations, contributed to tumor development, including significant islet cell adaptation in obesity-related tumors.
specifically, the researchers found abnormal cell expression of the peptide hormone intestinal trypsin peptides for obesity, and showed that islet expression of intestinal trypsin peptides promoted the formation of a malignant pancreatic catheter tumor driven by Kras.
, the researchers believe that the progression of PDAC is driven by changes associated with local obesity in the tumor micro-environment, which means that endocrine-exocrine signals are also involved in the development of PDAC in addition to insulin.
() Reference: Katherine Minjee Chung et al. Endocrine-Exocrine Signaling Drives Obesity-Associated Pancreatic Ductal Adenocarcinoma. Cell. 2020. doi:10.1016/j.cell.2020.03.06210.