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



Pubmed ID


Pubmed Central ID




Scopus ID

2-s2.0-84891893696   62 Citations


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


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, Newborn
Biological Factors
Breast Neoplasms
Cell Line, Tumor
Culture Media, Conditioned
Lung Neoplasms
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Neoplasm Invasiveness
Neoplasm Transplantation
Primary Cell Culture
Protease Inhibitors
Rats, Sprague-Dawley
Tumor Cells, Cultured