title: Epidermal growth factor (EGF)-enhanced vascular cell adhesion molecule-1 (VCAM-1) expression promotes macrophage and glioblastoma cell interaction and tumor cell invasion.
abstract: Activated EGF receptor (EGFR) signaling plays an instrumental role in glioblastoma (GBM) progression. However, how EGFR activation regulates the tumor microenvironment to promote GBM cell invasion remains to be clarified. Here, we demonstrate that the levels of EGFR activation in tumor cells correlated with the levels of macrophage infiltration in human GBM specimens. This was supported by our observation that EGFR activation enhanced the interaction between macrophages and GBM cells. In addition, EGF treatment induced up-regulation of vascular cell adhesion molecule-1 (VCAM-1) expression in a PKCε- and NF-κB-dependent manner. Depletion of VCAM-1 interrupted the binding of macrophages to GBM cells and inhibited EGF-induced and macrophage-promoted GBM cell invasion. These results demonstrate an instrumental role for EGF-induced up-regulation of VCAM-1 expression in EGFR activation-promoted macrophage-tumor cell interaction and tumor cell invasion and indicate that VCAM-1 is a potential molecular target for improving cancer therapy.
authors.affiliation: From the Brain Tumor Center and Department of Neuro-Oncology.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Zheng
authors.forename: Weiwei
authors.initials: W
authors.lastname: Yang
authors.forename: Kenneth
authors.initials: K
authors.lastname: Aldape
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Lu
mesh_terms: D002450:Cell Communication; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000235:genetics / Q000378:metabolism; D059016:Tumor Microenvironment / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D009363:Neoplasm Proteins; D019010:Vascular Cell Adhesion Molecule-1; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors; D051744:Protein Kinase C-epsilon
keywords: Epidermal Growth Factor Receptor (EGFR); Glioblastoma; Invasion; Macrophages; Migration
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