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Astrocytes directly influence tumor cell invasion and metastasis in vivo. PLoS One 2013;8(12):e80933

Date

12/11/2013

Pubmed ID

24324647

Pubmed Central ID

PMC3851470

DOI

10.1371/journal.pone.0080933

Scopus ID

2-s2.0-84891893696   48 Citations

Abstract

Brain metastasis is a defining component of tumor pathophysiology, and the underlying mechanisms responsible for this phenomenon are not well understood. Current dogma is that tumor cells stimulate and activate astrocytes, and this mutual relationship is critical for tumor cell sustenance in the brain. Here, we provide evidence that primary rat neonatal and adult astrocytes secrete factors that proactively induced human lung and breast tumor cell invasion and metastasis capabilities. Among which, tumor invasion factors namely matrix metalloprotease-2 (MMP-2) and MMP-9 were partly responsible for the astrocyte media-induced tumor cell invasion. Inhibiting MMPs reduced the ability of tumor cell to migrate and invade in vitro. Further, injection of astrocyte media-conditioned breast cancer cells in mice showed increased invasive activity to the brain and other distant sites. More importantly, blocking the preconditioned tumor cells with broad spectrum MMP inhibitor decreased the invasion and metastasis of the tumor cells, in particular to the brain in vivo. Collectively, our data implicate astrocyte-derived MMP-2 and MMP-9 as critical players that facilitate tumor cell migration and invasion leading to brain metastasis.

Author List

Wang L, Cossette SM, Rarick KR, Gershan J, Dwinell MB, Harder DR, Ramchandran R

Authors

Michael B. Dwinell PhD Director, Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin
Kevin Richard Rarick PhD Assistant Professor in the Pediatrics department at Medical College of Wisconsin
Ling Wang MD, PhD Assistant Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Animals, Newborn
Astrocytes
Biological Factors
Breast Neoplasms
Cell Line, Tumor
Culture Media, Conditioned
Female
Hippocampus
Humans
Lung Neoplasms
Male
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Mice
Neoplasm Invasiveness
Neoplasm Transplantation
Primary Cell Culture
Protease Inhibitors
Rats
Rats, Sprague-Dawley
Tumor Cells, Cultured
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d