Abstract
Purpose
We investigated the associations between hsMAD2 mRNA expression in tumor cells and sensitivity to paclitaxel or patient prognosis in neuroblastoma.
Methods
Fifty-one formalin-fixed paraffin-embedded tumor samples were manually microdissected to collect tumor cells, and RNA was purified. Nineteen clinical samples of advanced neuroblastoma showed appropriate quality of the isolated RNA for real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses. The hsMAD2 expression levels were determined by real-time RT-PCR in 4 neuroblastoma cell lines and 19 clinical samples. The sensitivity to paclitaxel was assessed by WST-8 colorimetric assays and flow cytometry. HsMAD2 expression of the clinical samples was investigated for its association with prognosis in advanced neuroblastoma patients.
Results
There was a significant positive correlation between hsMAD2 mRNA expression and the sensitivity to paclitaxel in four neuroblastoma cell lines. High hsMAD2 expression may be correlated with paclitaxel-induced apoptosis. Kaplan–Meier survival curves were stratified by hsMAD2 expression using the median value as a cut-off point and analyzed for prognostic significance by the log-rank test (P = 0.0467). Furthermore, multivariate survival analysis revealed that only hsMAD2 expression had a significant impact on the overall survival rate.
Conclusions
Our results may warrant clinical application of paclitaxel in neuroblastoma treatment for poor prognosis patients.
Similar content being viewed by others
References
Maris JM, Hogarty MD, Bagatell R, Cohn SL (2007) Neuroblastoma. Lancet 369(9579):2106–2120. doi:10.1016/S0140-6736(07)60983-0
Berthold F, Hero B (2000) Neuroblastoma: current drug therapy recommendations as part of the total treatment approach. Drugs 59(6):1261–1277
Goldsmith KC, Hogarty MD (2005) Targeting programmed cell death pathways with experimental therapeutics: opportunities in high-risk neuroblastoma. Cancer Lett 228(1–2):133–141. doi:10.1016/j.canlet.2005.01.048
Paffhausen T, Schwab M, Westermann F (2007) Targeted mycn expression affects cytotoxic potential of chemotherapeutic drugs in neuroblastoma cells. Cancer Lett 250(1):17–24. doi:10.1016/j.canlet.2006.09.010
Li Y, Benezra R (1996) Identification of a human mitotic checkpoint gene: hsMAD2. Science 274(5285):246–248
Kops GJ, Weaver BA, Cleveland DW (2005) On the road to cancer: aneuploidy and the mitotic checkpoint. Nat Rev Cancer 5(10):773–785. doi:10.1038/nrc1714
Hernando E, Nahle Z, Juan G, Diaz-Rodriguez E, Alaminos M, Hemann M, Michel L, Mittal V, Gerald W, Benezra R, Lowe SW, Cordon-Cardo C (2004) Rb inactivation promotes genomic instability by uncoupling cell cycle progression from mitotic control. Nature 430(7001):797–802. doi:10.1038/nature02820
Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT (1971) Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc 93(9):2325–2327
Kretschmar CS, Kletzel M, Murray K, Thorner P, Joshi V, Marcus R, Smith EI, London WB, Castleberry R (2004) Response to paclitaxel, topotecan, and topotecan–cyclophosphamide in children with untreated disseminated neuroblastoma treated in an upfront phase II investigational window: a pediatric oncology group study. J Clin Oncol 22(20):4119–4126. doi:10.1200/JCO.2004.08.174
Sudo T, Nitta M, Saya H, Ueno NT (2004) Dependence of paclitaxel sensitivity on a functional spindle assembly checkpoint. Cancer Res 64(7):2502–2508
Tanaka K, Nishioka J, Kato K, Nakamura A, Mouri T, Miki C, Kusunoki M, Nobori T (2001) Mitotic checkpoint protein hsMAD2 as a marker predicting liver metastasis of human gastric cancers. Jpn J Cancer Res 92(9):952–958
Tanaka K, Mohri Y, Ohi M, Yokoe T, Koike Y, Morimoto Y, Miki C, Tonouchi H, Kusunoki M (2008) Mitotic checkpoint genes, hsMAD2 and BubR1, in oesophageal squamous cancer cells and their association with 5-fluorouracil and cisplatin-based radiochemotherapy. Clin Oncol (R Coll Radiol) 20(8):639–646. doi:10.1016/j.clon.2008.06.010
Biedler JL, Helson L, Spengler BA (1973) Morphology and growth, tumorigenicity, and cytogenetics of human neuroblastoma cells in continuous culture. Cancer Res 33(11):2643–2652
Seeger RC, Rayner SA, Banerjee A, Chung H, Laug WE, Neustein HB, Benedict WF (1977) Morphology, growth, chromosomal pattern and fibrinolytic activity of two new human neuroblastoma cell lines. Cancer Res 37(5):1364–1371
Matsumura T, Sugimoto T, Sawada T, Amagai T, Negoro S, Kemshead JT (1987) Cell surface membrane antigen present on neuroblastoma cells but not fetal neuroblasts recognized by a monoclonal antibody (KP-NAC8). Cancer Res 47(11):2924–2930
Sugimoto T, Horii Y, Hino T, Kemshead JT, Kuroda H, Sawada T, Morioka H, Imanishi J, Inoko H (1989) Differential susceptibility of HLA class II antigens induced by gamma-interferon in human neuroblastoma cell lines. Cancer Res 49(7):1824–1828
Kisenge RR, Toyoda H, Kang J, Tanaka S, Yamamoto H, Azuma E, Komada Y (2003) Expression of short-form caspase 8 correlates with decreased sensitivity to Fas-mediated apoptosis in neuroblastoma cells. Cancer Sci 94(7):598–605
Toyoda H, Ido M, Hayashi T, Gabazza EC, Suzuki K, Kisenge RR, Kang J, Hori H, Komada Y (2004) Experimental treatment of human neuroblastoma using live-attenuated poliovirus. Int J Oncol 24(1):49–58
Tanaka K, Otake K, Mohri Y, Ohi M, Yokoe T, Toiyama Y, Miki C, Tonouchi H, Kusunoki M (2009) Clinical significance of the gene expression profile in residual tumor cells after neoadjuvant chemo-radiotherapy for esophageal cancer. Oncol Rep 21(6):1489–1494
Bijwaard KE, Aguilera NS, Monczak Y, Trudel M, Taubenberger JK, Lichy JH (2001) Quantitative real-time reverse transcription-PCR assay for cyclin D1 expression: utility in the diagnosis of mantle cell lymphoma. Clin Chem 47(2):195–201
Ogawa M, Hori H, Ohta T, Onozato K, Miyahara M, Komada Y (2005) Sensitivity to gemcitabine and its metabolizing enzymes in neuroblastoma. Clin Cancer Res 11(9):3485–3493. doi:10.1158/1078-0432.CCR-04-1781
Surico G, Muggeo P, De Leonardis F, Rigillo N (2003) New paclitaxel–cisplatin based chemotherapy regimen for advanced stage, recurrent, or refractory neuroblastoma—preliminary report. Med Pediatr Oncol 40(2):130–132. doi:10.1002/mpo.10106
Ramanathan RK, Rubin JT, Ohori NP, Belani CP (2000) Dramatic response of adult wilms tumor to paclitaxel and cisplatin. Med Pediatr Oncol 34(4):296–298. doi:10.1002/(SICI)1096-911X(200004)34:4<296:AID-MPO20>3.0.CO
Italiano A, Sirvent N, Michiels JF, Peyrade F, Otto J, Thyss A (2005) Tumour response to paclitaxel in an adult with relapsed nephroblastoma. Lancet Oncol 6(4):252–253. doi:10.1016/S1470-2045(05)70098-X
Li Z, Zhang J, Liu Z, Woo CW, Thiele CJ (2007) Downregulation of Bim by brain-derived neurotrophic factor activation of TrkB protects neuroblastoma cells from paclitaxel but not etoposide or cisplatin-induced cell death. Cell Death Differ 14(2):318–326. doi:10.1038/sj.cdd.4401983
Jiang BH, Liu LZ (2008) Role of mtor in anticancer drug resistance: Perspectives for improved drug treatment. Drug Resist Updat 11(3):63–76. doi:10.1016/j.drup.2008.03.001
Conflict of interest
Authors declare no potential financial disclosure or conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Otake, K., Uchida, K., Tanaka, K. et al. HsMAD2 mRNA expression may be a predictor of sensitivity to paclitaxel and survival in neuroblastoma. Pediatr Surg Int 27, 217–223 (2011). https://doi.org/10.1007/s00383-010-2780-5
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00383-010-2780-5