CXCR4 mediates the proliferation of glioblastoma progenitor cells.
Increasing evidence points to a fundamental role for cancer stem cells (CSC) in the initiation and propagation of many tumors. As such, in the context of glioblastoma multiforme (GBM), the development of treatment strategies specifically targeted towards CSC-like populations may hold significant therapeutic promise. To this end, we now report that the cell surface chemokine receptor, CXCR4, a known mediator of cancer cell proliferation and invasion, is overexpressed in primary glioblastoma progenitor cells versus corresponding differentiated tumor cells. Furthermore, administration of CXCL12, the only known ligand for CXCR4, stimulates a specific and significant proliferative response in progenitors but not differentiated tumor cells. Taken together, these results implicate an important role for the CXCR4 signaling mechanism in glioma CSC biology and point to the therapeutic potential of targeting this pathway in patients with GBM.
Ehtesham
Moneeb
M
Department of Neurological Surgery, Vanderbilt University Medical Center, 21st Avenue & Garland Street, Nashville, TN 37232, USA. moneeb.ehtesham@vanderbilt.edu
Mapara
Khubaib Y
KY
Stevenson
Charles B
CB
Thompson
Reid C
RC
D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000502:physiology; D017931:DNA Primers; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D019718:Receptors, CXCR4 / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000473:pathology
C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D017931:DNA Primers; D019718:Receptors, CXCR4