Homing of colorectal cancer (CRC) cells to the liver is a non-random process driven by a crosstalk between tumour 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 tumoural 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 coexpressed α6 integrin and E-cadherin in primary tumours represent a poor prognostic factor for patients with advanced CRC.
A complex of α(6) integrin and E-cadherin drives liver metastasis of colorectal cancer cells through hepatic angiopoietin-like 6 / Marchiò S;Soster M;Cardaci S;Muratore A;Bartolini A;Barone V;Ribero D;Monti M;Bovino P;Sun J;Giavazzi R;Asioli S;Cassoni P;Capussotti L;Pucci P;Bugatti A;Rusnati M;Pasqualini R;Arap W;Bussolino F. - In: EMBO MOLECULAR MEDICINE. - ISSN 1757-4676. - STAMPA. - 4:11(2012), pp. 1156-1175. [10.1002/emmm.201101164]
A complex of α(6) integrin and E-cadherin drives liver metastasis of colorectal cancer cells through hepatic angiopoietin-like 6.
ASIOLI, SOFIA;
2012
Abstract
Homing of colorectal cancer (CRC) cells to the liver is a non-random process driven by a crosstalk between tumour 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 tumoural 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 coexpressed α6 integrin and E-cadherin in primary tumours represent a poor prognostic factor for patients with advanced CRC.File | Dimensione | Formato | |
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