Expression of the chemokine ligand Fractalkine in human colorectal cancer

Principal Investigator: Dr Paola Allavena

Department: Immunology and Inflammation

Institution: Humanitas Clinical and Research Center, Humanitas University, Italy

Key words: chemokines, Fractalkine, macrophages, T lymphocytes, metastases

In this study we investigated the expression of the trans-membrane chemokine CX3CL1 and its specific receptor CX3CR1 by human colorectal cancer cells. We found that CX3CL1 and CX3CR1 are upregulated and heterogeneously expressed by tumor cells. Patients with concomitant low expression of CX3CL1 and CX3CR1 (axis- negative) have significantly shorter disease-free and disease specific survival. In particular, the CX3CL1-CX3CR1 axis seems to play an important role in the metastatic process, since axis-negative tumors show a dramatic increased risk of developing metachronous distant-organ metastases. Notably, tumor cells at metastatic sites expressed significantly lower levels of both ligand and receptor. Our experimental results demonstrate that tumor cells bearing this chemokine axis have enhanced paracrine cell-cell adhesion, forming aggregates that reduced their migratory ability. In human CRC, low tumoral expression of CX3CL1 and CX3CR1 identifies a subset of patients at higher risk of tumor recurrence with distant metastasis, needing closer post-surgical surveillance.