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The CCL2-CCR2 astrocyte-cancer cell axis in tumor extravasation at the brain.

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.

SUBMITTER: Hajal C

PROVIDER: S-EPMC8221620 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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The CCL2-CCR2 astrocyte-cancer cell axis in tumor extravasation at the brain.

Hajal Cynthia C Shin Yoojin Y Li Leanne L Serrano Jean Carlos JC Jacks Tyler T Kamm Roger D RD

Science advances 20210623 26

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 astr ...[more]

PMID: 34162553

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