title: Exogenous IGFBP-2 promotes proliferation, invasion, and chemoresistance to temozolomide in glioma cells via the integrin β1-ERK pathway.
abstract: BACKGROUND
  Insulin-like growth factor binding protein-2 (IGFBP-2) is significantly increased in the serum of patients with malignant gliomas. High plasma IGFBP-2 levels are correlated with poor prognosis in glioma patients. However, the exact role of exogenous IGFBP-2 in gliomas is unclear.
  
  
  RESULTS
  Using the MTT cell viability assay, cell cycle analysis, and the transwell migration assay, it was demonstrated that IGFBP-2 treatment stimulated proliferation and invasion in U87 and U251 cell lines and primary SU3 glioma cells. Western blot analysis and immunofluorescence staining revealed that IGFBP-2 promoted ERK phosphorylation and nuclear translocation. Moreover, blocking ERK activation using the inhibitor PD98059 markedly reduced the effects of IGFBP-2 in glioma cells. As IGFBP-2 has an integrin-binding domain, the contribution of integrin β1 to these IGFBP-2-mediated processes was examined. Neutralisation or knockdown of the expression of integrin β1 inhibited IGFBP-2-induced ERK activation, cell proliferation, and cell invasion. Significantly, IGFBP-2 induced temozolomide resistance in glioma cells in an integrin β1/ERK-dependent manner.
  
  
  CONCLUSIONS
  Exogenous IGFBP-2 induces proliferation, invasion, and chemoresistance in glioma cells via integrin β1/ERK signaling, suggesting that targeting this pathway could represent a potential therapeutic strategy for the treatment of gliomas. The identification of this pathway in glioma progression provides insight into the mechanism by which serum IGFBP-2 levels can predict the prognosis of glioma patients.
authors.affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Nanjing Street 155, Heping District, Shenyang 110001, China.
authors.forename: S
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Nanjing Street 155, Heping District, Shenyang 110001, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Nanjing Street 155, Heping District, Shenyang 110001, China.
authors.forename: L M
authors.initials: LM
authors.lastname: Master
authors.affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Nanjing Street 155, Heping District, Shenyang 110001, China.
authors.forename: Z W
authors.initials: ZW
authors.lastname: Master
authors.affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Nanjing Street 155, Heping District, Shenyang 110001, China.
authors.forename: A
authors.initials: A
authors.lastname: Wu
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000502:physiology*; D019012:Integrin beta1 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D009361:Neoplasm Invasiveness; D000077204:Temozolomide; D046888:Tissue Array Analysis
chemical_list: D018906:Antineoplastic Agents, Alkylating; C577903:IGFBP2 protein, human; D018971:Insulin-Like Growth Factor Binding Protein 2; D019012:Integrin beta1; D003606:Dacarbazine; D048049:Extracellular Signal-Regulated MAP Kinases; D000077204:Temozolomide
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