Epidermal growth factor receptor-transfected bone marrow stromal cells exhibit enhanced migratory response and therapeutic potential against murine brain tumors

Cancer Gene Ther. 2005 Sep;12(9):757-68. doi: 10.1038/sj.cgt.7700827.


We have created a novel cellular vehicle for gene therapy of malignant gliomas by transfection of murine bone marrow stroma cells (MSCs) with a cDNA encoding epidermal growth factor receptor (EGFR). These cells (EGFR-MSCs) demonstrate enhanced migratory responses toward glioma-conditioned media in comparison to primary MSCs in vitro. Enhanced migration of EGFR-MSC was at least partially dependent on EGF-EGFR, PI3-, MAP kinase kinase, and MAP kinases, protein kinase C, and actin polymerization. Unlike primary MSCs, EGFR-MSCs were resistant to FasL-mediated cytotoxicity and were capable of stimulating allogeneic mixed lymphocyte reaction, suggesting EGFR-MSCs possess suitable characteristics as vehicles for brain tumor immuno-gene therapy. Following injection at various sites, including the contralateral hemisphere in the brain of syngeneic mice, EGFR-MSCs were able to migrate toward GL261 gliomas or B16 melanoma in vivo. Finally, intratumoral injection with EGFR-MSC adenovirally engineered to secrete interferon-alpha to intracranial GL261 resulted in significantly prolonged survival in comparison to controls. These data indicate that EGFR-MSCs may serve as attractive vehicles for infiltrating brain malignancies such as malignant gliomas.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism
  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / physiology*
  • Brain Neoplasms / therapy*
  • Cell Line
  • Cell Movement*
  • Epidermal Growth Factor / metabolism
  • ErbB Receptors / genetics*
  • Genetic Therapy / methods*
  • Glioma / therapy*
  • Mice
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Kinase C / metabolism
  • Stromal Cells / physiology
  • Transfection


  • Actins
  • Epidermal Growth Factor
  • Phosphatidylinositol 3-Kinases
  • ErbB Receptors
  • Protein Kinase C