Abstract 1741: Quantitative Real-Time PCR analysis of SPARCL1 and SPARC expression in colorectal cancer tissues

Abstract

Abstract The SPARC family of proteins comprises 10 members, which share structural similarities in one or more protein domains. SPARC-like protein 1 (SPARCL1; also known as hevin) and SPARC are two important family members, which have been found to be involved in various tumors. The relationship between these two molecules and colorectal cancer and its liver metastasis has not yet been fully studied and understood. cDNA microarray was used to analyze the expression profiles of 22523 genes in CC531 rat colon adenocarcinoma cells. Briefly, 2 × 106 CC531 were injected into the portal vein of male Wag/Rij rats to grow in the liver. The tumor cells were then re-isolated from rat livers at different time points (after 3, 6, 9, 14 and 21 days). SPARCL 1 and SPARC were among the genes, which were up-regulated in the re-isolated metastatic cells as compared to control CC531 cells grown in vitro, especially on days 3 (two- and nine-fold for SPARCL1 and SPARC) and 6 (four- and eleven-fold for SPARCL1 and SPARC) following tumor implantation. These results motivated us to analyze the expression of these two genes in 65 colorectal cancer tissues taken from patients in different UICC tumor stages (I, n=11; II, n=23; III, n=17; IV, n=14). A mixture of 10 mucosa samples was taken for comparison as normal control. Quantitative real time-PCR results showed that SPARCL1 mRNA was significantly down-regulated in 44 samples (68%) with these levels being on average fourfold lower (0.24 ± 0.21) than those in normal mucosa. Normal levels were found in 18 samples (28%), and up-regulated levels were detected in only 3 samples (4%) with these levels being on average threefold higher than those in normal mucosa (3.0 ± 1.1). No correlation between this down- or up-regulation and tumor stage could be found. In contrast to the results for SPARCL1, SPARC showed an almost consistent up-regulation in 60 of the tumor samples (92%). The average level of SPARC up-regulation was higher than that of SPARCL1 (6.5 fold higher than in normal mucosa). It is worth noting here that in those 21 samples, in which SPARCL1 mRNA was not down-regulated, SPARC expression was on average twofold higher (13fold higher than in normal mucosa) than the average expression level of all samples. These results suggest a relationship between the two family members, but it is still not clear, whether they have opposing or complementary functions in the context of tumor initiation and progression. More studies should be performed to uncover the possible role of these proteins in the course of colorectal cancer and its liver metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1741.