Abstract
Abstract Introduction: Changes in lipid biosynthesis has attracted significant attention in the study of cancer. Its value in our understanding of pancreatic cancer has not yet been realized. This study examined lysophosphatidic acid (LPA) variant biosynthesis in patients with stage II-III pancreatic ductal adenocarcinoma (PDAC), evaluating serum, bile, and tissue levels of LPA, its receptors, and downstream metabolites. LPA, a product of phospholipase D activity of the enzyme autotaxin (ATX) is a potent mitogenic agent. Data suggests that changes in lipid biosynthesis contribute to the tumor microenvironment in PDAC. Methods: PDAC, matched adjacent non-malignant tissues, gall bladder bile and serum samples were collected from patients with Stage II-III pancreatic cancer at the time of surgery. Control bile and serum were collected from patients undergoing cholecystectomy for benign disease and living renal donors respectively. Results: Serum and biliary LPA levels were increased in patients with PDAC when compared to controls. ATX activity, and LPA receptors, LPAR1, LPAR2, and LPAR5 were greater in PDAC adjacent pancreatic tissue when compared to PDAC tissue. In contrast, TNFα receptors TNFα1 and TNFα2 and LPA receptor LPAR3 receptor expression was greater in PDAC lesions when compared to adjacent tissue. Conclusion: PDAC patients display a modified LPA biosynthesis profile, when compared to non-PDAC patients, potentially providing a paracrine-signaling cascade to promote pancreatic tumorigenesis through increased expression of mitogenic cytokines and growth factors. Citation Format: Nicholas J. Skill, Mary A. Maluccio. Lysophosphatidic acid receptor signaling and pancreatic adenocarcinoma tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4941. doi:10.1158/1538-7445.AM2017-4941
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