Chemokine receptor CXCR4: What is its role in gastrointestinal cancer?

Abstract

e14687 Background: Multiple metastasis is the predominant cause of colorectal cancer (CC) and pancreatic cancer (PC) related mortality. Chemokines receptors have been implicated in cancer metastatic process by directing the migration of tumour cells to sites of metastasis. However, their clinical relevance in gastrointestinal cancer has not been defined. The aim of our study was to evaluate the possible role of CXCR4 as prognostic factor in CC and PC. Methods: Quantitative determination of CXCR4 in serum samples were collected before and after surgery from 36 CC and 23 PC patients later treated with adjuvant (Ad) therapy or for metastatic (Meta) disease (19 Ad-and 17 Meta-CC; 15Ad-PC and 8 Meta-PC) and from 31 healthy controls (HC) enrolled as controls group, was performed by means of ELISA. Relative expression levels of CXCR4 in matched-pairs of tumour and adjacent normal tissue samples collected from the same 36 CC and 15 Ad-PC patients, were determined by means of qRT-PCR using the QuantiFast SYBR Green PCR kit. Results: Compared to HC, pre-operative CXCR4 serum levels were increased in both CC and PC patients. Post-operative serum levels were higher than those observed pre-operatively in 42% and 47% of patients with Ad- and Meta-CC, respectively. Conversely, in 53% and 50% of patients with Ad- and Meta-PC, CXCR4 serum levels decreased after surgical treatment. Furthermore, higher levels of CXCR4 were associated with advanced stages and in PC with lymph nodes involvement. In addition, CXCR4 was over-expressed in tumor compared to normal tissue in 42% and 41% of patients with Ad- and Meta-CC, and in 73% of patients with Ad-PC. In relation to clinical phenotype, all these patients had stage T3N1 disease in both disease. Conclusions: Our data showed that CXCR4 levels may be associated with tumor stage and disease progression in CC and PC patients. Further studies with larger samples size, might confirm the role for CXCR4 as prognostic factor and/or marker of patients’ response to therapy.