Chemokines regulate colon cancer metastasis

Abstract: Background: Chemokines are small molecular weight proteins, which mainly function as a chemoattractant cytokines for leukocyte migration. Emerging data indicate that chemokines may also play a role in cancer biology. Colon cancer is one of the most leading causes of death especially in the industrial world. The most common causes of mortality are due to the metastasis of colon cancer. Aim: The aim of the study was to understand how chemokines may contribute to colon cancer metastasis. Materials and Method: Chemokine receptors CXCR (CXCR4, CXCR3, CXCR7) and CCR receptors (CCR4, CCR6, CCR7, CCR8) mRNA expression were evaluated by Real Time – Polymerase Chain Reaction (RT-PCR) in HT29 and 19/97' colon cancer cell lines. Following gene expression, flowcytometry was used to assess chemokine receptors protein expression. Finally, functional receptors were verified in both cell lines using a migration assay with their corresponding ligands. Results: Both cell lines expressed all chemokine receptors mRNA except CXCR7 with the highest expression being detected for CXCR4, CXCR3 and CCR4. Flowcytometry for the expressed receptors also revealed protein surface expression. The chemokine ligands TARC/CCL17 and SDF-1/CXCL12 induced a significant increase in colon cancer cell migration in a dose- and time- dependent manner. Conclusions: Our data demonstrate increased expression of functional CCR4, CXCR3, and CXCR4 in colon cancer cells, suggesting that their chemokine ligands might be involved in the regulation of colon cancer metastasis.