P036. SPARC affects colorectal tumourigenesis
K. Fu1, F. Lloyd1, C. Forrest2, B. Klopcic1, I. Lawrance1, 1University of Western Australia, Centre for Inflammatory Bowel Disesases, Medicine and Pharmacology, Perth, Australia, 2University of Western Australia, Pathology and Laboratory Medicine, Perth, Australia
Colorectal cancer (CRC) is common but its clinical risk could be reduced by improvement in the understanding of its pathogenesis. The aim of this study was determine the potential of secreted protein, acidic and rich in cysteine (SPARC) to impact the development of colorectal tumours by identifying differences in gene expression levels and inflammatory cell infiltration in a chronic-inflammation induced model of tumourogenesis in SPARC knockout (KO) and wild-type (WT) mice.
Colitis-associated tumourgenesis was promoted in SPARC-KO and WT mice by a single intraperitoneal injection of azoxymethane prior to three cycles of 7 days of dextran sodium sulphate. Tumour size, number and overall tumour burden was assessed endoscopically and histologically. Immunofluorescent (IF) assessment of CD4, CD8a, CD68, F4/80 and Ki-67 were performed on tumours. Tumours of similar size were harvested from both models at week 11 and processed for microsarray analysis. Whole-genome microarray (Illumina BeadChip, MouseRef 8 v2) compared gene expression in tumours from both genotypes.
All tumours were dysplastic tubular adenomas with focal high-grade dysplasia but SPARC-KO mice had a lower tumour burden than WT animals. IF assessment of the inflammatory cell infiltrates showed CD4-positive, CD8a-positive, CD68-positive and F4/80-positive cells in all tumours without any significant differences between the models. KO tumours had higher numbers of KI-67+ve cells but this was not significant. Microarray analysis identified 6 differentially regulated genes between KO and WT mice (p < 0.05), 4 were decreased in KO tumours and were involved in the regulation of the immune response (Ifit2, Ido), cell growth and proliferation (Areg, Hoxa7). Two genes were increased in KO tumours with one associating with apoptosis (Erdr1) and one with an unknown function (Hamp2).
Differences in gene expression were identified between SPARC-KO and WT tumours and these may impact on differences in tumour development and burden but not inflammatory cell infiltration.