Homing of colorectal cancer (CRC) cells to the liver is a nonrandom process driven by a crosstalk between tumor cells and components of the host tissue. Here we report the isolation of a liver metastasis-specific peptide ligand (CGIYRLRSC) that binds a complex of E-cadherin and α6 integrin on the surface of CRC cells. We identify angiopoietin-like 6 protein as a peptide-mimicked natural ligand enriched in hepatic blood vessels of CRC patients. We demonstrate that an interaction between hepatic angiopoietin-like 6 and tumoral α6 integrin/E-cadherin drives liver homing and colonization by CRC cells, and that CGIYRLRSC inhibits liver metastasis through interference with this ligand/receptor system. Our results indicate a mechanism for metastasis whereby a soluble factor accumulated in normal vessels functions as a specific ligand for circulating cancer cells. Consistently, we show that high amounts of coincident α6 integrin and E-cadherin in primary tumors represent a poor prognostic factor for patients with advanced CRC
A complex of α6 integrin and E-cadherin drives the liver metastasis of colorectal cancer cells by a physical and functional interaction with hepatic angiopoietin-like 6
MARCHIO', Serena;SOSTER, MARCO;ASIOLI, Sofia;CASSONI, Paola;BUSSOLINO, Federico
2012-01-01
Abstract
Homing of colorectal cancer (CRC) cells to the liver is a nonrandom process driven by a crosstalk between tumor cells and components of the host tissue. Here we report the isolation of a liver metastasis-specific peptide ligand (CGIYRLRSC) that binds a complex of E-cadherin and α6 integrin on the surface of CRC cells. We identify angiopoietin-like 6 protein as a peptide-mimicked natural ligand enriched in hepatic blood vessels of CRC patients. We demonstrate that an interaction between hepatic angiopoietin-like 6 and tumoral α6 integrin/E-cadherin drives liver homing and colonization by CRC cells, and that CGIYRLRSC inhibits liver metastasis through interference with this ligand/receptor system. Our results indicate a mechanism for metastasis whereby a soluble factor accumulated in normal vessels functions as a specific ligand for circulating cancer cells. Consistently, we show that high amounts of coincident α6 integrin and E-cadherin in primary tumors represent a poor prognostic factor for patients with advanced CRCFile | Dimensione | Formato | |
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