Dual role of autotaxin as novel biomarker and therapeutic target in pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms (panNENs) are rare pancreatic neoplasms, and descriptions of treatment remain limited. Autotaxin (ATX) is a secreted autocrine motility factor involved in the production of lysophosphatidic acid (LPA), a lipid mediator that promotes the progression of various cancers. The aim of this study was to clarify the importance of the ATX-LPA axis in panNENs and to confirm its contribution to panNEN progression using clinical data, cell lines, and a mouse model. Serum ATX level was higher in patients with panNEN than in patients with other pancreatic diseases (chronic pancreatitis, pancreatic ductal adenocarcinoma [PDAC], intraductal papillary mucinous neoplasm, autoimmune pancreatitis) and healthy controls, and 61% of clinical specimens stained strongly for ATX. In a case we encountered, serum ATX level fluctuated with disease progression. An in vitro study showed higher ATX mRNA expression in panNEN cell lines than in PDAC cell lines. Cell proliferation and migration in panNEN cell lines were stimulated via the ATX-LPA axis and suppressed by RNA interference or inhibitors. An in vivo study showed that intraperitoneal injection of GLPG1690, an ATX inhibitor, suppressed tumor progression in a xenograft model. These findings revealed that ATX expression is significantly elevated in panNEN and is related to the progression of panNEN. We showed the potential of ATX as a novel biomarker and therapeutic target. Autotaxin (ATX), which is a secreted autocrine motility factor involved in the production of a lipid mediator, was highly expressed in pancreatic endocrine neoplasm (panNEN). The mRNA expression of mRNA in panNEN cell lines was higher than in pancreatic ductal adenocarcinoma cell lines. The serum level of ATX in panNEN patients was higher than in patients with other pancreatic diseases, and in immunohistochemical analysis of panNEN, tumor cells were stained strongly by ATX.image

Automated summary

This study demonstrates the significant elevation of autotaxin (ATX) expression in pancreatic neuroendocrine neoplasms (panNENs) and its association with panNEN progression. Through clinical data, cell lines, and a mouse model, the researchers confirm the involvement of the ATX-LPA axis in promoting cell proliferation and migration in panNENs. These findings suggest the potential of ATX as a novel biomarker and therapeutic target for panNENs.