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Transcriptional profiling comparing S100PBP over-expressing human FA6 pancreatic cancer cells to vector-only control FA6 cells

ABSTRACT: "S100PBP is significantly down-regulated in pancreatic cancer compared to normal samples. The functional roles of S100PBP are unknown, and therefore, profiling cells over-expressing this gene may lead to further understanding of its functional mechanisms. We have performed microarray gene expression analysis of FA6 cells over-expressing S100PBP to vector-only control cells to gain clues on the cellular functions of S100PBP."

ORGANISM(S): Homo sapiens

SUBMITTER: Chelala Claude

PROVIDER: S-ECPF-GEOD-35198 | biostudies-other |

REPOSITORIES: biostudies-other

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Project description:Purpose: Core 3 derived glycans, a major type of O-glycan expressed by normal epithelial cells of the gastrointestinal tract, are downregulated during malignancy, because of loss of expression of functional β3-N-acetylglucosaminyltransferase-6 (core 3 synthase). We investigated the expression of core 3 synthase in normal pancreas and pancreatic cancer and evaluated the biological effects of re-expressing core 3 synthase in pancreatic cancer cells that had lost expression. Experimental Design: We determined that pancreatic tumors and tumor cell lines have lost expression of core 3 synthase. We therefore re-expressed in human pancreatic cancer cells (Capan-2 and FG) to investigate the contribution of core 3 glycans to malignant progression. Results: Pancreatic cancer cells expressing core 3 synthase showed reduced in vitro cell proliferation, migration and invasion compared with vector control cells. Expression of core 3 O-glycans induced altered expression of β1 integrin, decreased activation of focal adhesion kinase, led to the down regulation of expression of several genes including REG1α and FGFR3, and altered lamellipodia formation. The addition of a GlcNAc residue by core 3 synthase leads to the extension of the tumor associated Tn structure on MUC1. Orthotopic injection of FG cells expressing core 3 synthase into the pancreas of nude mice produced significantly smaller tumors and decreased metastasis to the surrounding tissues compared to vector control FG cells. Conclusions: These findings indicate that expression of core 3 derived O-glycans in pancreatic cancer cells suppresses tumor growth and metastasis through modulation of glycosylation of mucins and other cell surface and extracellular matrix proteins. Two-condition experiment, Core 3 synthase stable expression (C3) vs. vector control (PLVX) cells. Biological replicates: 3 Core 3 synthase stable expression, 3 vector control, independently grown and harvested. One replicate per array.

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Transcriptional profiling comparing S100PBP over-expressing human FA6 pancreatic cancer cells to vector-only control FA6 cells

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