A complex of α 6 integrin and E‐cadherin drives liver metastasis of colorectal cancer cells through hepatic angiopoietin‐like 6

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 α 6 integrin on the...

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Published in:EMBO molecular medicine 2012-11, Vol.4 (11), p.1156-1175
Main Authors: Marchiò, Serena, Soster, Marco, Cardaci, Sabrina, Muratore, Andrea, Bartolini, Alice, Barone, Vanessa, Ribero, Dario, Monti, Maria, Bovino, Paola, Sun, Jessica, Giavazzi, Raffaella, Asioli, Sofia, Cassoni, Paola, Capussotti, Lorenzo, Pucci, Piero, Bugatti, Antonella, Rusnati, Marco, Pasqualini, Renata, Arap, Wadih, Bussolino, Federico
Format: Article
Language:English
Subjects:
Angiogenesis
Angiopoietin
Bioinformatics
Blood vessels
Cancer therapies
Cell adhesion & migration
Colonization
Colorectal cancer
Colorectal carcinoma
Experiments
Gene expression
Grants
Hepatocytes
Industrial research
Kinases
Library collections
Ligands
Liver
Liver cancer
Medical prognosis
Medical research
Metastases
Metastasis
Peptides
Proteomics
Tumors
Variance analysis
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Summary: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 α 6 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 α 6 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 α 6 integrin and E‐cadherin in primary tumours represent a poor prognostic factor for patients with advanced CRC.
ISSN:1757-4676
1757-4684
DOI:10.1002/emmm.201101164