Astrocytes directly influence tumor cell invasion and metastasis in vivo. PLoS One 2013;8(12):e80933
Date
12/11/2013Pubmed ID
24324647Pubmed Central ID
PMC3851470DOI
10.1371/journal.pone.0080933Scopus ID
2-s2.0-84891893696 (requires institutional sign-in at Scopus site) 76 CitationsAbstract
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 RAuthors
Michael B. Dwinell PhD Director, Professor in the Microbiology and Immunology department at Medical College of WisconsinRamani 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
MESH terms used to index this publication - Major topics in bold
AnimalsAnimals, 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