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Gene Expression Profile of Metastatic Human Pancreatic Cancer Cells Depends on the Organ Microenvironment

Departments of ¹ Cancer Biology and ² Biostatistics and Applied Mathematics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Isaiah J. Fidler, Department of Cancer Biology, Unit 173, The University of Texas M.D. Anderson Cancer Center, P.O. Box 302429, Houston, TX 77230-1429. Phone: 713-792-8580; Fax: 713-792-8747; E-mail: ifidler{at}mdanderson.org.

To determine the influence of the microenvironment on changes in gene expression, we did microarray analysis on three variant lines of a human pancreatic cancer (FG, L3.3, and L3.6pl) with different metastatic potentials. The variant lines were grown in tissue culture in the subcutis (ectopic) or pancreas (orthotopic) of nude mice. Compared with tissue culture, the number of genes of which the expression was affected by the microenvironment was up-regulated in tumors growing in the subcutis and pancreas. In addition, highly metastatic L3.6pl cells growing in the pancreas expressed significantly higher levels of 226 genes than did the L3.3 or FG variant cells. Growth of the variant lines in the subcutis did not yield similar results, indicating that the orthotopic microenvironment significantly influences gene expression in pancreatic cancer cells. These data suggest that investigations of the functional consequence of gene expression require accounting for experimental growth conditions. [Cancer Res 2007;67(1):139–48]