title: Differential expression of CXCR4 and CXCR7 with various stem cell markers in paired human primary and recurrent glioblastomas.
abstract: The chemokine CXCL12 (also termed SDF-1, stromal cell-derived factor-1) and its receptors CXCR4 and CXCR7 are known to play a pivotal role in tumor progression including glioblastomas (GBM). Previous investigations focused on the expression and functional roles of CXCR4 and CXCR7 in different GBM cell subpopulations, but comparative analysis in matched primary versus recurrent GBM samples are still lacking. Thus, here we investigated the expression of CXCR4 and CXCR7 on mRNA and protein level using matched primary and recurrent GBM pairs. Additionally, as GBM CXCR4-positive stem-like cells are supposed to give rise to recurrence, we compared the expression of both receptors in primary and recurrent GBM cells expressing either neural (MUSASHI-1) or embryonic stem cell markers (KLF-4, OCT-4, SOX-2, NANOG). We were able to show that both CXCR4 and CXCR7 were expressed at considerable mRNA and protein levels. CXCR7 was downregulated in relapse cases, and different groups regarding CXCR4/CXCR7 expression differences between primary and recurrent samples could be distinguished. A co-expression of both receptors was rare. In line with this, CXCR4 was co-expressed with all investigated neural and embryonic stem cell markers in both primary and recurrent tissues, whereas CXCR7 was mostly found on stem cell marker-negative cells, but was co-expressed with KLF-4 on a distinct GBM cell subpopulation. These results point to an individual role of CXCR4 and CXCR7 in stem cell marker-positive GBM cells in glioma progression and underline the opportunity to develop new therapeutic tools for GBM intervention.
authors.affiliation: Department of Neurosurgery, University Medical Center Schleswig-Holstein UKSH, Campus Kiel, D-24105 Kiel, Germany.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Flüh
authors.affiliation: Department of Anatomy, University of Kiel, D-24118 Kiel, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Hattermann
authors.affiliation: Department of Neurosurgery, University Medical Center Schleswig-Holstein UKSH, Campus Kiel, D-24105 Kiel, Germany.
authors.forename: H Maximilian
authors.initials: HM
authors.lastname: Mehdorn
authors.affiliation: Department of Neurosurgery, University Medical Center Schleswig-Holstein UKSH, Campus Kiel, D-24105 Kiel, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Synowitz
authors.affiliation: Department of Neurosurgery, University Medical Center Schleswig-Holstein UKSH, Campus Kiel, D-24105 Kiel, Germany.
authors.forename: Janka
authors.initials: J
authors.lastname: Held-Feindt
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D000071317:Nanog Homeobox Protein / Q000096:biosynthesis; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis; D054387:Receptors, CXCR / Q000096:biosynthesis* / Q000235:genetics; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis
chemical_list: C501896:ACKR3 protein, human; D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; D051741:Kruppel-Like Transcription Factors; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C080774:erythroid Kruppel-like factor