Muscle and adipose transcriptome in a mouse model of cachexia induced by orthotopic pancreatic cancer, with and without tumor-derived interleukin-6 (IL-6)

Pancreatic ductal adenocarcinoma (PDAC) causes involuntary wasting of adipose and muscle tissue, also known as cachexia. Cachexia is a major cause of cancer-related deaths, particularly among patients with PDAC. Here we profiled gene expression in adipose tissue and skeletal muscle in normal/sham control mice and in mice bearing orthotopic PDAC tumors. PDAC tumors were initiated by intra-pancreatic injection of a cell line derived from the KPC (Kras-G12D;Trp-R172H;Pdx1::Cre) genetically engineered mouse model of pancreatic cancer, or by injection of the same cell line deleted for the IL6 gene using CRISPR/Cas9. KPC-IL6 knockout (ko) cells caused less adipose wasting and no muscle loss compared with KPC-wildtype (wt) cells. Overall design: 8-week old C57BL6/J male mice were subjected to surgery without (sham) or with implantation of tumor cells by direct injection into the pancreas. All mice were kept until the KPC group demonstrated overt wasting, upon which time all mice were euthanized. mRNA was isolated from quadriceps muscles or from the epididymal fat pads for RNAseq. Muscle and fat samples came from separate sets of mice.