Differential expression of genes in tumor cells growing in the peripheral and central zones of pancreatic cancer

825

Gene expression analysis using cDNA microarray can be a useful tool to predict the potential progression of Neoplasms. Since all tumors are biologically heterogeneous, we wished to determine whether gene expression will differ between cells growing in the central zone and cells growing in the peripheral zone of tumors. Cells in non-necrotic central area and periphery of human pancreatic cancer growing in the pancreas of nude mice were isolated by Laser Capture Microdissection. Total RNA was extracted and gene expression profiles were compared using Affymetrix HG-U133-Plus-2.0 array, which containing 54,674 probe sets. Comparison of gene expression pattern in central zone tumor cells and peripheral zone tumor cells identified statistical difference in 86 genes, of which 58 were up-regulated in the peripheral and 28 were up-regulated in the central zone of the pancreatic tumors. Among the genes up-regulated in the peripheral zone were genes functionally characterized by protease activity, changes in cell morphology, invasiveness, tumor cell-stroma interaction, proliferation and metastasis. Examples are: protease serine 23, fibronectin 1, Integrin beta6, galectin 1, collagen type III alpha1, and chemokine C-X-CR4. The up-regulation of genes expressed in tumor cells residing in the central zone or peripheral zone were confirmed by in situ hybridization analysis. These data demonstrate that different areas within a Neoplasms from which clinical samples are collected for studies of gene expression present different profile i.e. individual Neoplasms can present a heterogenous profile of gene expression. Whether the differential expression between cells growing in the peripheral zone versus central zone is now under active investigation.