title: Cord blood stem cells inhibit epidermal growth factor receptor translocation to mitochondria in glioblastoma.
abstract: BACKGROUND
  Overexpression of EGFR is one of the most frequently diagnosed genetic aberrations of glioblastoma multiforme (GBM). EGFR signaling is involved in diverse cellular functions and is dependent on the type of preferred receptor complexes. EGFR translocation to mitochondria has been reported recently in different cancer types. However, mechanistic aspects of EGFR translocation to mitochondria in GBM have not been evaluated to date.
  
  
  RESULTS
  In the present study, we analyzed the expression of EGFR in GBM-patient derived specimens using immunohistochemistry, reverse-transcription based PCR and Western blotting techniques. In clinical samples, EGFR co-localizes with FAK in mitochondria. We evaluated this previous observation in standard glioma cell lines and in vivo mice xenografts. We further analyzed the effect of human umbilical cord blood stem cells (hUCBSC) on the inhibition of EGFR expression and EGFR signaling in glioma cells and xenografts. Treatment with hUCBSC inhibited the expression of EGFR and its co-localization with FAK in glioma cells. Also, hUCBSC inhibited the co-localization of activated forms of EGFR, FAK and c-Src in mitochondria of glioma cells and xenografts. In addition, hUCBSC also inhibited EGFR signaling proteins in glioma cells both in vitro and in vivo.
  
  
  CONCLUSIONS
  We have shown that hUCBSC treatments inhibit phosphorylation of EGFR, FAK and c-Src forms. Our findings associate EGFR expression and its localization to mitochondria with specific biological functions in GBM cells and provide relevant preclinical information that can be used for the development of effective hUCBSC-based therapies.
authors.affiliation: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Illinois, United States of America.
authors.forename: Venkata Ramesh
authors.initials: VR
authors.lastname: Dasari
authors.forename: Kiran Kumar
authors.initials: KK
authors.lastname: Velpula
authors.forename: Kiranmai
authors.initials: K
authors.lastname: Alapati
authors.forename: Meena
authors.initials: M
authors.lastname: Gujrati
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Tsung
mesh_terms: D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D066246:ErbB Receptors / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D010766:Phosphorylation; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000502:physiology*; D019061:src-Family Kinases
chemical_list: D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases; C000631346:CSK protein, human