Identification and causes of metabonomic difference between orthotopic and subcutaneous xenograft of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal tumors. However, the methodological differences between orthotopic and subcutaneous xenograft (OX and SX) models will cause confusion in understanding its pathological mechanism and clinical relevance. In this study, SX and OX models were established by implanting Panc-1 and BxPC-3 cell strains under skin and on the pancreas of mice, respectively. The tumor tissue and serum samples were collected for(1)H NMR spectroscopy followed by univariate and multivariate statistical analyses. As results, no obvious metabonomic difference was demonstrated in serum between the two models, however, the model- and cell strain-specific metabonomic differences were observed in tumor tissues. According to the KEGG analysis, ABC transporters, glycerophospholipid metabolism, purine metabolism and central carbon metabolism were identified to be the most significant components involved in metabonomic differences. Considering the methodological discrepancy in SX and OX models, such differences should be contributed to tumor microenvironment. In general, SX are not equivalent to OX models at molecular level. Subcutaneous transplantation displayed its inherent limitations though it offered a simple, inexpensive, reproducible and quantifiable advantage. And orthotopic transplantation may be favorable to simulate PDAC in patients due to its similar pathogenesis to human pancreatic cancer.