Liver Metastasis Is Facilitated by the Adherence of Circulating Tumor Cells to Vascular Fibronectin Deposits

The interaction between circulating tumor cells (CTC) and endothelial cells during extravasation is a critical process during metastatic colonization, but its mechanisms remain poorly characterized. Here we report that the luminal side of liver blood vessels contains fibronectin deposits that are en...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2017-07, Vol.77 (13), p.3431-3441
Main Authors: Barbazán, Jorge, Alonso-Alconada, Lorena, Elkhatib, Nadia, Geraldo, Sara, Gurchenkov, Vasily, Glentis, Alexandros, van Niel, Guillaume, Palmulli, Roberta, Fernández, Beatriz, Viaño, Patricia, Garcia-Caballero, Tomas, López-López, Rafael, Abal, Miguel, Vignjevic, Danijela Matic
Format: Article
Language:English
Subjects:
Animals
Blood vessels
Cancer
Cell adhesion
Cell adhesion & migration
Cell Adhesion - physiology
Cell Line, Tumor
Colonization
Deposits
Endothelial cells
Endothelium
Extravasation
Fibronectin
Fibronectins - metabolism
Humans
Liver
Liver Neoplasms - blood
Liver Neoplasms - pathology
Metastases
Metastasis
Mice
Mice, Nude
Neoplasm Metastasis
Neoplastic Cells, Circulating - pathology
Transendothelial and Transepithelial Migration
Tumor cells
Tumors
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Summary:The interaction between circulating tumor cells (CTC) and endothelial cells during extravasation is a critical process during metastatic colonization, but its mechanisms remain poorly characterized. Here we report that the luminal side of liver blood vessels contains fibronectin deposits that are enriched in mice bearing primary tumors and are also present in vessels from human livers affected with metastases. Cancer cells attached to endothelial fibronectin deposits via talin1, a major component of focal adhesions. Talin1 depletion impaired cancer cell adhesion to the endothelium and transendothelial migration, resulting in reduced liver metastasis formation Talin1 expression levels in patient CTC's correlated with prognosis and therapy response. Together, our findings uncover a new mechanism for liver metastasis formation involving an active contribution of hepatic vascular fibronectin and talin1 in cancer cells. .
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-16-1917