Journal of Neuro-Oncology

, Volume 106, Issue 1, pp 89–98

Growth-inhibitory effect of neurotrophin-3-secreting adipose tissue-derived mesenchymal stem cells on the D283-MED human medulloblastoma cell line

  • Young-Hoon Kim
  • Seung Hee Cho
  • Soo Jung Lee
  • Seung Ah Choi
  • Ji Hoon Phi
  • Seung-Ki Kim
  • Kyu-Chang Wang
  • Byung-Kyu Cho
  • Chae-Yong Kim
Laboratory Investigation - Human/Animal Tissue

Abstracts

Medulloblastoma (MBL), the most common malignant pediatric brain tumor, is incurable in about one-third of patients and can lead to long-term disabilities despite current multimodal treatments. The purpose of this study was to demonstrate in vitro biological effects of neurotrophins-3 (NT-3) on MBL cells and to evaluate the growth-inhibitory effect of neurotrophin-3 (NT-3)-secreting stem cells on tumor cells. We confirmed by western blotting that D283-MED cells express tyrosine kinase C, a specific receptor for NT-3. Analyzing the biological effects of NT-3 on MBL cells, we evaluated autophagy, apoptosis, senescence, and differentiation of tumor cells with NT-3. The NT-3 induced a concentration-dependent increase in apoptosis in the tumor cell line (P < 0.001). The high concentrations of NT-3 increased the expression of class III β-tubulin (P < 0.001) and decreased the expression of Nestin (P < 0.05). NT-3-secreting stem cells were produced by nucleofecting pIRES2.EGFP-NT3 into human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) and their tropic property toward MBL cells was confirmed by migration assay. Double-layered co-culture experiments with the NT-3-secreting hAT-MSCs and D283-MED MBL cells were performed, and NT-3-induced cell death was studied by 3-(4,5-dimethylathiazol-2-yl)-2,5-dephenyl-tetrazolium bromide (MTT) assay. Consequently, the high concentrations of NT-3-secreting hAT-MSCs significantly (P < 0.05) increased the death of D283-MED cells in vitro. The present study demonstrated that both apoptotic cell death and neuronal differentiation of tumor cells were the mechanisms of growth-inhibitory effect of NT-3-secreting hAT-MSCs on MBL cell line.

Keywords

Neurotrophin-3 Adipose tissue-derived mesenchymal stem cell Medulloblastoma Apoptosis Differentiation 

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Young-Hoon Kim
    • 1
    • 2
  • Seung Hee Cho
    • 3
  • Soo Jung Lee
    • 3
  • Seung Ah Choi
    • 4
  • Ji Hoon Phi
    • 1
    • 4
  • Seung-Ki Kim
    • 1
    • 4
  • Kyu-Chang Wang
    • 1
    • 4
  • Byung-Kyu Cho
    • 1
    • 4
  • Chae-Yong Kim
    • 1
    • 3
  1. 1.Department of NeurosurgerySeoul National University College of MedicineSeoulKorea
  2. 2.Department of NeurosurgerySeoul National University HospitalSeoulKorea
  3. 3.Department of NeurosurgerySeoul National University Bundang HospitalSeongnam-siKorea
  4. 4.Division of Pediatric NeurosurgerySeoul National University Children’s HospitalSeoulKorea

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