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01.01.2012 | Laboratory Investigation - Human/Animal Tissue

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

verfasst von: 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

Erschienen in: Journal of Neuro-Oncology | Ausgabe 1/2012

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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.

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Titel: Growth-inhibitory effect of neurotrophin-3-secreting adipose tissue-derived mesenchymal stem cells on the D283-MED human medulloblastoma cell line
verfasst von: 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
Publikationsdatum: 01.01.2012
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 1/2012
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-011-0656-8

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