CXCR4 chemokine receptor mediates melanoma and colorectal cancer metastasis to the liver

Abstract Introduction: Chemokine receptors have been identified as potential factors in organ-specific metastasis of multiple cancers. Since both melanoma and colorectal cancer (CRC) metastasize to the liver, we hypothesized that similar chemokine receptors facilitate liver metastasis of both cancers. Methods: Patients with resection for metastatic liver disease (n = 16, melanoma; n=22, CRC) were selected from a database. Initially, screening microarrays for chemokine receptors were analyzed using primary and metastatic cell lines and frozen tissues. Upon identifying chemokine receptors common to both cancers, validation studies were conducted in cell lines and formalin-fixed paraffin embedded liver metastasis specimens (FFPE). RNA was extracted and assessed by quantitative real-time polymerase chain reaction (qRT). Migration assays using melanoma and CRC cell lines were performed to determine if CXCR4 receptor was functional. Results: Screening microarrays identified CXCR4 as the most common chemokine receptor. qRT of cancer cell lines and 38 FFPE demonstrated CXCR4 expression in the cell lines (n = 5/6) and 81% (n = 13/16) and 100% (n = 22) of FFPE in melanoma and CRC, respectively. Migration studies demonstrated 5- and 3-fold increases in response to SDF-1 (CXCL12), the ligand to CXCR4, for melanoma and CRC, respectively, over controls (p Conclusions: CXCR4 is expressed in melanoma and CRC liver metastasis and is functional in both melanoma and CRC cell lines. The liver, which highly produces SDF-1, is a selective target for CXCR4 (+) melanoma and CRC cells. These studies suggest that CXCR4 may serve a key role in progression of liver metastasis of both cancers.