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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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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
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cited_by cdi_FETCH-LOGICAL-c502t-8edd498ab8c1c10faed1d7de995563a54693afdf3222286466a4beee458502e33
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container_end_page 3441
container_issue 13
container_start_page 3431
container_title Cancer research (Chicago, Ill.)
container_volume 77
creator 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
description 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. .
doi_str_mv 10.1158/0008-5472.can-16-1917
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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
title Liver Metastasis Is Facilitated by the Adherence of Circulating Tumor Cells to Vascular Fibronectin Deposits
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