Role of Tumor Microenvironment on Gene Expression in Pancreatic Cancer Tumor Models

Abstract

The microenvironment is known to be a relevant factor of influence on tumor growth and metastasis in pancreatic ductal adenocarcinoma (PDAC). To determine the influence of the microenvironment on changes in gene expression, we analyzed gene expression in different PDAC tissues. Four human PDAC cell lines were introduced into a murine PDAC model with two insertion techniques: injection and implantation. Gene expression profiles of the cell lines growing in vitro and in vivo (ectopically and orthotopically) were established by microarray and validated by RT-PCR. Significant differences were found in the gene expression profiles of the in vitro versus in vivo tissues (P < 0.05), while no differences were found between the in vivo tissues. Analyzing the orthotopic tumors derived from the injection and implantation methods, similar gene expression patterns with 0%-18% significantly differentially expressed genes between tumors of the two different methods were observed (analysis of variance [ANOVA]; P < 0.0001). Gene expression from cell lines growing in vitro differed from the expression patterns of the same cells growing in vivo, while the localization of the growing tumor cells did not significantly alter gene expression. These data demonstrate that the implantation and injection techniques used in this study yield similar results and may be compared with each other.