Role of tumor microenvironment on gene expression in pancreatic cancer tumor models

TY - JOUR

T1 - Role of tumor microenvironment on gene expression in pancreatic cancer tumor models

AU - Mees, Soeren Torge

AU - Mardin, Wolf Arif

AU - Schleicher, Christina

AU - Colombo-Benkmann, Mario

AU - Senninger, Norbert

AU - Haier, Joerg

N1 - Copyright © 2011 Elsevier Inc. All rights reserved.

PY - 2011/11

Y1 - 2011/11

N2 - OBJECTIVES: 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.METHODS: 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.RESULTS: 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).CONCLUSIONS: 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.

AB - OBJECTIVES: 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.METHODS: 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.RESULTS: 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).CONCLUSIONS: 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.

KW - Adenocarcinoma

KW - Animals

KW - Carcinoma, Pancreatic Ductal

KW - Cell Line, Tumor

KW - Disease Models, Animal

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Male

KW - Mice

KW - Mice, Nude

KW - Neoplasm Transplantation

KW - Oligonucleotide Array Sequence Analysis

KW - Pancreatic Neoplasms

KW - Tumor Microenvironment

U2 - 10.1016/j.jss.2010.03.034

DO - 10.1016/j.jss.2010.03.034

M3 - SCORING: Journal article

C2 - 20605603

VL - 171

SP - 136

EP - 142

JO - J SURG RES

JF - J SURG RES

SN - 0022-4804

IS - 1

ER -