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The CCL2-CCR2 astrocyte-cancer cell axis in tumor extravasation at the brain
Name
eabg8139.full.pdf
Description
Published version
Size
9.68 MB
Format
Adobe PDF
Checksum (MD5)
a8362b341e7c5242443f852113c79a69
Author(s)
Hajal, Cynthia
Shin, Yoojin
Li, Leanne
Serrano, Jean Carlos
Jacks, Tyler
Kamm, Roger D
Date Issued
2021
Journal
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Version
Final published version
Abstract
Although brain metastases are common in cancer patients, little is known about the mechanisms of cancer extravasation across the blood-brain barrier (BBB), a key step in the metastatic cascade that regulates the entry of cancer cells into the brain parenchyma. Here, we show, in a three-dimensional in vitro BBB microvascular model, that astrocytes promote cancer cell transmigration via their secretion of C-C motif chemokine ligand 2 (CCL2). We found that this chemokine, produced primarily by astrocytes, promoted the chemotaxis and chemokinesis of cancer cells via their C-C chemokine receptor type 2 (CCR2), with no notable changes in vascular permeability. These findings were validated in vivo, where CCR2-deficient cancer cells exhibited significantly reduced rates of arrest and transmigration in mouse brain capillaries. Our results reveal that the CCL2-CCR2 astrocyte-cancer cell axis plays a fundamental role in extravasation and, consequently, metastasis to the brain.
Terms of Use
Creative Commons Attribution NonCommercial License 4.0
Persistent DSpace Link
DOI of Published Version
10.1126/sciadv.abg8139
