A novel pre-clinical in vivo mouse model for malignant brain tumor growth and invasion.
Glioblastoma multiforme (GBM) is a rapidly progressive disease of morbidity and mortality and is the most common form of primary brain cancer in adults. Lack of appropriate in vivo models has been a major roadblock to developing effective therapies for GBM. A new highly invasive in vivo GBM model is described that was derived from a spontaneous brain tumor (VM-M3) in the VM mouse strain. Highly invasive tumor cells could be identified histologically on the hemisphere contralateral to the hemisphere implanted with tumor cells or tissue. Tumor cells were highly expressive for the chemokine receptor CXCR4 and the proliferation marker Ki-67 and could be identified invading through the pia mater, the vascular system, the ventricular system, around neurons, and over white matter tracts including the corpus callosum. In addition, the brain tumor cells were labeled with the firefly luciferase gene, allowing for non-invasive detection and quantitation through bioluminescent imaging. The VM-M3 tumor has a short incubation time with mortality occurring in 100% of the animals within approximately 15 days. The VM-M3 brain tumor model therefore can be used in a pre-clinical setting for the rapid evaluation of novel anti-invasive therapies.
Shelton
Laura M
LM
Boston College, Higgins Hall 140 Commonwealth Ave, Chestnut Hill, MA 02467, USA.
Mukherjee
Purna
P
Huysentruyt
Leanne C
LC
Urits
Ivan
I
Rosenberg
Joshua A
JA
Seyfried
Thomas N
TN
D000818:Animals; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D007124:Immunoenzyme Techniques; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
C514936:CXCR4 protein, mouse; D018971:Insulin-Like Growth Factor Binding Protein 2; D012333:RNA, Messenger; D019718:Receptors, CXCR4