Increased dietary fatty acids determine the fatty-acid profiles of human pancreatic cancer cells and their carrier's plasma, pancreas and liver.

Primary contents of dietary fat are three or four types of fatty acids, namely saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), n6-polyunsaturated fatty acid (n6PUFA) and, to less extent, n3-polyunsaturated fatty acid (n3PUFA). Previous studies suggest that increased SFA, MUFA, and n6PUFA in high fat diets (HFDs) stimulate the origination, growth, and liver metastasis of pancreatic cancer cells, whereas increased n3PUFA has the opposite effects. It is unclear whether the fatty acid-induced effects are based on changed fatty-acid composition of involved cells. Here, we investigated whether increased SFA, MUFA, n6PUFA, and n3PUFA in different HFDs determine the FA profiles of pancreatic cancer cells and their carrier's plasma, pancreas, and liver. We transplanted MiaPaCa2 human pancreatic cancer cells in athymic mice and fed them normal diet or four HFDs enriched with SFA, MUFA, n6PUFA, and n3PUFA, respectively. After 7 weeks, fatty acids were profiled in tumor, plasma, pancreas, and liver, using gas chromatography. When tumor carriers were fed four HFDs, the fatty acids that were increased dietarily were also increased in the plasma. When tumor carriers were fed MUFA-, n6PUFA-, and n3PUFA-enriched HFDs, the dietarily increased fatty acids were also increased in tumor, pancreas, and liver. When tumor-carriers were fed the SFA-enriched HFD featuring lauric and myristic acids (C12:0 and C14:0), tumor, ‍pancreas, and liver showed an increase not in the same SFAs but palmitic acid (C16:0) and/or stearic acid (C18:0). In ‍conclusion, predominant fatty acids in HFDs determine the fatty-acid profiles of pancreatic cancer cells and their murine ‍carriers.

[1]  R. Luben,et al.  Dietary oleic acid is inversely associated with pancreatic cancer - Data from food diaries in a cohort study. , 2018, Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.].

[2]  Lijuan Hu,et al.  The Warburg effect in human pancreatic cancer cells triggers cachexia in athymic mice carrying the cancer cells , 2018, BMC Cancer.

[3]  M. Foti,et al.  Omega-3 Fatty Acids Protect Fatty and Lean Mouse Livers After Major Hepatectomy , 2017, Annals of surgery.

[4]  M. Hashizume,et al.  Extra-pancreatic invasion induces lipolytic and fibrotic changes in the adipose microenvironment, with released fatty acids enhancing the invasiveness of pancreatic cancer cells , 2017, Oncotarget.

[5]  P. Stepnowski,et al.  Hyper-Elongation in Colorectal Cancer Tissue – Cerotic Acid is a Potential Novel Serum Metabolic Marker of Colorectal Malignancies , 2017, Cellular Physiology and Biochemistry.

[6]  Feng Wang,et al.  Four types of fatty acids exert differential impact on pancreatic cancer growth. , 2015, Cancer letters.

[7]  Lijun Xu,et al.  Jinlida granule inhibits palmitic acid induced-intracellular lipid accumulation and enhances autophagy in NIT-1 pancreatic β cells through AMPK activation. , 2015, Journal of ethnopharmacology.

[8]  Yu Hu,et al.  SREBP1 regulates tumorigenesis and prognosis of pancreatic cancer through targeting lipid metabolism , 2015, Tumor Biology.

[9]  M. Fernández,et al.  Dietary strategies to reduce metabolic syndrome , 2013, Reviews in Endocrine and Metabolic Disorders.

[10]  M. Darabi,et al.  Tissue fatty acid composition in human urothelial carcinoma , 2013, British journal of biomedical science.

[11]  T. Krechler,et al.  Plasma Fatty Acid Composition in Patients with Pancreatic Cancer: Correlations to Clinical Parameters , 2012, Nutrition and cancer.

[12]  T. Sugimura,et al.  Enhancement of Carcinogenesis and Fatty Infiltration in the Pancreas in N-Nitrosobis(2-Oxopropyl)Amine-Treated Hamsters by High-Fat Diet , 2011, Pancreas.

[13]  T. Adrian,et al.  Alteration of strain background and a high omega‐6 fat diet induces earlier onset of pancreatic neoplasia in EL‐Kras transgenic mice , 2011, International journal of cancer.

[14]  E. Holly,et al.  Intake of fatty acids and antioxidants and pancreatic cancer in a large population‐based case‐control study in the San Francisco Bay Area , 2010, International journal of cancer.

[15]  J. Permert,et al.  Increased lipid metabolism and cell turnover of MiaPaCa2 cells induced by high-fat diet in an orthotopic system. , 2009, Metabolism: clinical and experimental.

[16]  D. Silverman,et al.  Dietary fatty acids and pancreatic cancer in the NIH-AARP diet and health study. , 2009, Journal of the National Cancer Institute.

[17]  M. Washington,et al.  Tumorigenesis and Neoplastic Progression High Fat Diet Induced Hepatic Steatosis Establishes a Permissive Microenvironment for Colorectal Metastases and Promotes Primary Dysplasia in a Murine Model , 2010 .

[18]  E. Herrera,et al.  Influence of Fatty Acid Profile of Total Parenteral Nutrition Emulsions on the Fatty Acid Composition of Different Tissues of Piglets , 2008, Lipids.

[19]  H. Reber,et al.  Opposing Effects of n-6 and n-3 Polyunsaturated Fatty Acids on Pancreatic Cancer Growth , 2008, Pancreas.

[20]  H. Guski,et al.  Influence of Different Dietary Fat Intake on Liver Metastasis and Hepatic Lipid Peroxidation in BOP-Induced Pancreatic Cancer in Syrian Hamsters , 2006, Pancreatology.

[21]  H. Sampath,et al.  The fate and intermediary metabolism of stearic acid , 2005, Lipids.

[22]  E. Martínez-Victoria,et al.  Dietary-induced changes in the fatty acid profile of rat pancreatic membranes are associated with modifications in acinar cell function and signalling. , 2004, The British journal of nutrition.

[23]  P. Dagnelie,et al.  Fatty acid composition of plasma lipids in patients with pancreatic, lung and oesophageal cancer in comparison with healthy subjects. , 2002, Clinical nutrition.

[24]  M. Arends,et al.  Apoptotic death of pancreatic cancer cells induced by polyunsaturated fatty acids varies with double bond number and involves an oxidative mechanism , 1998, The Journal of pathology.

[25]  K. Fearon,et al.  Effect of eicosapentaenoic acid and other fatty acids on the growth in vitro of human pancreatic cancer cell lines. , 1994, British Journal of Cancer.

[26]  R. Woutersen,et al.  Effects of dietary linoleic acid on pancreatic carcinogenesis in rats and hamsters. , 1994, Cancer research.

[27]  N. Habib,et al.  Effects of dietary fatty acids on the early stages of neoplastic induction in the rat pancreas. Changes in fatty acid composition and development of atypical acinar cell nodules. , 1991, International journal of experimental pathology.

[28]  J. Kinsella,et al.  Effect of dietary omega-3 and omega-6 fatty acids on development of azaserine-induced preneoplastic lesions in rat pancreas. , 1989, Journal of the National Cancer Institute.

[29]  L. Braden,et al.  Fat and cancer , 1986, Cancer.

[30]  T. Adrian,et al.  A high omega-3 fatty acid diet mitigates murine pancreatic precancer development. , 2011, The Journal of surgical research.

[31]  M. Walz,et al.  Does enteral nutrition of dietary polyunsaturated fatty acids promote oxidative stress and tumour growth in ductal pancreatic cancer? Experimental trial in Syrian Hamster. , 2006, Prostaglandins, leukotrienes, and essential fatty acids.

[32]  T. Adrian,et al.  Effects of high-fat diet and cholecystokinin receptor blockade on promotion of pancreatic ductal cell tumors in the hamster. , 1997, Nutrition and cancer.