CXCR4 mRNA expression in colon, esophageal and gastric cancers and hepatitis C infected liver

We have recently demonstrated by Northern blot and RT-PCR that the mRNA exp ression of the alpha-chemokine hIRH/SDF-1 alpha is reduced in hepatocellula r carcinoma (HCC), several digestive tract cancers and premalignant colon a denomas, and that its receptor CXCR4 mRNA expression is reduced in HCC. Her e we investigate the expression of CXCR3 mRNA expression in several digesti ve tract cancers and hepatitis C viral (HCV) infected liver, a premalignant condition. There was no difference in the CXCR4 mRNA expression in colon, esophageal or gastric cancers compared to non-cancerous tissues. This is si gnificantly different from the reduced expression we have seen with hepatoc ellular carcinoma (p<0.05). To better refine regional tumor or hepatic cyto kine mRNA analysis within a biopsy sample we describe a micro-isolation tec hnique for RNA extraction from portal and triad areas of liver biopsies of other small malignant or non-malignant biopsy samples suitable for use in R T-PCR and differential display reactions. In HCV liver biopsies, the expres sion of hIRH and its receptor CXCR4 mRNA, corrected for G3PDH, was not sign ificantly different from that of control non-HCV (steatosis) biopsies. CXCR 3 is expressed on leukocytes and its expression was predicted to correlate with hepatic inflammation. CXCR4 receptor mRNA expression did correlate sig nificantly with that of its ligand hIRH/SDF-1 alpha (p=0.001), and with the severity of fibrosis (p<0.05), but not with portal inflammation (p<0.10), piecemeal necrosis (p<0.10), lobular inflammation (p>0.10), the presence of lymphoid aggregates (p>0.10), or the total histological activity index (p= 0.07). There was no difference in expression of hIRH or CXCR3 between respo nders and non-responders to interferon (IFN) treatment, while as a control, the responder group of patients did show a higher expression of IFN alpha receptor than the non-responder group (p=0.05).