MMP9 Clears the Way for Metastatic Cell Penetration Across the Blood-Brain Barrier

Authors

Joseph H McCarty

Publication Date

4-14-2023

Journal

Cancer Research

DOI

10.1158/0008-5472.CAN-23-0151

PMID

37057598

PMCID

PMC11696691

PubMedCentral® Posted Date

1-3-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Although brain metastases are 10-fold more prevalent than primary brain cancers, relatively little is understood about the genes and pathways that promote metastatic cell entry, growth, and survival in the brain. Hence, determining how metastatic tumors colonize the brain and thrive within the neural microenvironment is a topic of both fundamental importance and direct clinical relevance. In this issue, a report by Karreman and colleagues explores pathways that are exploited by metastatic tumor cells to arrest in the circulation, cross the endothelial blood-brain barrier (BBB), and thrive in the brain microenvironment. The authors used elegant imaging tools including intravital fluorescence microcopy and serial reconstruction of ultrastructural sections to analyze BBB breach and subsequent colonization of the brain. They show that matrix metalloprotease 9 (MMP9) plays a central role in these events. Pharmacologic or genetic targeting of MMP9 significantly reduced penetration across the BBB and limited micrometastasis formation. Surprisingly, extravasation and brain colonization does not involve significant degradation of canonical MMP9 protein targets such as collagen and laminin in vascular basement membranes, indicating the requirement for other extracellular matrix (ECM) or non-ECM substrates for MMP9. Collectively, these new and important findings reveal cell-cell adhesion and signaling events between cerebral endothelial and metastatic cancer cells as well as identify potential therapeutic targets to prevent metastatic tumor cell dissemination in the brain. See related article by Karreman et al., p. 1299.

Keywords

Humans, Blood-Brain Barrier, Endothelium, Vascular, Matrix Metalloproteinase 9, Brain, Cell Line, Tumor, Neoplasms

Published Open-Access

yes

Recommended Citation

Joseph H McCarty, "MMP9 Clears the Way for Metastatic Cell Penetration Across the Blood-Brain Barrier" (2023). Faculty, Staff and Student Publications. 4809.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4809