Obesity-Induced Inflammation and Desmoplasia Promote Pancreatic Cancer Progression and Resistance to Chemotherapy

• Published in: Cancer discovery Vol. 6; no. 8; pp. 852 - 869
• Main Authors: Incio, Joao, Liu, Hao, Suboj, Priya, Chin, Shan M., Chen, Ivy X., Pinter, Matthias, Ng, Mei R., Nia, Hadi T., Grahovac, Jelena, Kao, Shannon, Babykutty, Suboj, Huang, Yuhui, Jung, Keehoon, Rahbari, Nuh N., Han, Xiaoxing, Chauhan, Vikash P., Martin, John D., Kahn, Julia, Huang, Peigen, Desphande, Vikram, Michaelson, James, Michelakos, Theodoros P., Ferrone, Cristina R., Soares, Raquel, Boucher, Yves, Fukumura, Dai, Jain, Rakesh K.
• Format: Journal Article
• Language: English
• Published: United States 01.08.2016
• Subjects: Adipose Tissue - metabolism; Angiotensin II Type 1 Receptor Blockers - pharmacology; Animals; Body Mass Index; Carcinoma, Pancreatic Ductal - drug therapy; Carcinoma, Pancreatic Ductal - pathology; Combined Modality Therapy; Diet, High-Fat - adverse effects; Disease Models, Animal; Disease Progression; Drug Resistance, Neoplasm - drug effects; Fibrosis; Genetic Predisposition to Disease; Humans; Inflammation - etiology; Inflammation - pathology; Interleukin-1beta - metabolism; Male; Mice; Mice, Knockout; Models, Biological; Neutrophils - immunology; Neutrophils - metabolism; Obesity - complications; Obesity - etiology; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - etiology; Pancreatic Neoplasms - pathology; Receptor, Angiotensin, Type 1 - metabolism; Signal Transduction - drug effects; Tumor Burden; Tumor Microenvironment

It remains unclear how obesity worsens treatment outcomes in patients with pancreatic ductal adenocarcinoma (PDAC). In normal pancreas, obesity promotes inflammation and fibrosis. We found in mouse models of PDAC that obesity also promotes desmoplasia associated with accelerated tumor growth and imp...