Top

Child's Nervous System

Published in:

01-12-2012 | Original Paper

Establishment and characterization of xenograft models of human neuroblastoma bone metastasis

Authors: Hongyu Zhao, Weisong Cai, Shuai Li, Zuke Da, Hanxue Sun, Liang Ma, Yaoxin Lin, Debao Zhi

Published in: Child's Nervous System | Issue 12/2012

Abstract

Objects

To improve the therapy of advanced neuroblastoma (NB), it is critical to develop animal models that mimic NB bone metastases. Unlike the human disease, NB xenograft models rarely metastasize spontaneously to bone from the orthotopic site of primary tumor growth.

Methods

Single-cell suspensions of SY5Y, KCNR NB cells were injected directly into the femur of nude mice. Radiological and histological analyses and immunohistochemistry analyses were performed to characterize these osseous NB models. SY5Y and KCNR result in osteolytic responses.

Results

We have detected osteoprotegerin, receptor activator of nuclear factor kappa B ligand, parathyroid hormone-related protein, and endothelin-1, proteins associated with bone growth and osteolysis, and C-X-C chemokine receptor type 4 (CXCR4) involved in tumor growth and tumor cell migration in the NB cells grown in the bone.

Conclusions

These animal models can be used to study biological interactions, pathways, and potential therapeutic targets and also to evaluate new agents for treatment and prevention of NB bone metastasis.

Ara T, DeClerck YA (2006) Mechanisms of invasion and metastasis in human neuroblastoma. Cancer Metastasis Rev 25:645–657PubMedCrossRef

Bilir A, Erguven M, Yazihan N, Aktas E, Oktem G, Sabanci A (2010) Enhancement of vinorelbine-induced cytotoxicity and apoptosis by clomipramine and lithium chloride in humanneuroblastoma cancer cell line SH-SY5Y. J Neurooncol 100:385–395PubMedCrossRef

Carlisle AJ, Lyttle CA, Carlisle RY, Maris JM (2009) CXCR4 expression heterogeneity in neuroblastoma cells due to ligand-independent regulation. Mol Cancer 8:126PubMedCrossRef

Dickey A, Schleicher S, Leahy K, Hu R, Hallahan D, Thotala DK (2011) GSK-3β inhibition promotes cell death, apoptosis, and in vivo tumor growth delay in neuroblastoma Neuro-2A cell line. J Neurooncol 104:145–153PubMedCrossRef

Dubois SG, Kalika Y, Lukens JN, Brodeur GM, Seeger RC, Atkinson JB, Haase GM, Black CT, Perez C, Shimada H, Gerbing R, Stram DO, Matthay KK (1999) Metastatic sites in stage IV and IVS neuroblastoma correlate with age, tumor biology, and survival. J Pediatr Hematol Oncol 21:181–189PubMedCrossRef

Feng C, Zuo Z (2012) Regulatory factor X1-induced down-regulation of transforming growth factor β2 transcription in human neuroblastoma cells. J Biol Chem 287:22730–22739PubMedCrossRef

Granchi D, Corrias MV, Garaventa A, Baglìo SR, Cangemi G, Carlini B, Paolucci P, Giunti A, Baldini N (2011) Neuroblastoma and bone metastases: clinical significance and prognostic value of Dickkopf 1 plasma levels. Bone 48:152–159PubMedCrossRef

Granchi D, Garaventa A, Amato I, Paolucci P, Baldini N (2006) Plasma levels of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in patients with neuroblastoma. Int J Cancer 119:146–151PubMedCrossRef

Hua Y, Gorshkov K, Yang Y, Wang W, Zhang N, Hughes DP (2012) Slow down to stay alive: HER4 protects against cellular stress and confers chemoresistance in neuroblastoma. Cancer. doi:10.1002/cncr.27496

10.

Kroesen M, Lindau D, Hoogerbrugge P, Adema GJ (2012) Immunocombination therapy for high-risk neuroblastoma. Immunotherapy 4:163–174PubMedCrossRef

11.

Li W, Chu Y, Zhang L, Yin L, Li L (2012) Ginsenoside Rg1 prevents SK-N-SH neuroblastoma cell apoptosis induced by supernatant from Aβ(1-40)-stimulated THP-1 monocytes. Brain Res Bull 88:501–506PubMedCrossRef

12.

Ma M, Ye JY, Deng R, Dee CM, Chan GC (2011) Mesenchymal stromal cells may enhance metastasis of neuroblastoma via SDF-1/CXCR4 and SDF-1/CXCR7 signaling. Cancer Lett 312:1–10PubMedCrossRef

13.

Maris JM, Hogarty MD, Bagatell R, Cohn SL (2007) Neuroblastoma. Lancet 369:2106–2120PubMedCrossRef

14.

Matthay KK, George RE, Yu AL (2012) Promising therapeutic targets in neuroblastoma. Clin Cancer Res 18:2740–2753PubMedCrossRef

15.

Meier R, Mühlethaler-Mottet A, Flahaut M, Coulon A, Fusco C, Louache F, Auderset K, Bourloud KB, Daudigeos E, Ruegg C, Vassal G, Gross N, Joseph JM (2007) The chemokine receptor CXCR4 strongly promotes neuroblastoma primary tumour and metastatic growth, but not invasion. PLoS One 2:e1016PubMedCrossRef

16.

Owens C, Irwin M (2012) Neuroblastoma: the impact of biology and cooperation leading to personalized treatments. Crit Rev Clin Lab Sci 49:85–115PubMedCrossRef

17.

Park JR, Eggert A, Caron H (2008) Neuroblastoma: biology, prognosis, and treatment. Pediatr Clin North Am 55:97–120PubMedCrossRef

18.

Patel LR, Camacho DF, Shiozawa Y, Pienta KJ, Taichman RS (2011) Mechanisms of cancer cell metastasis to the bone: a multistep process. Future Oncol 7:1285–1297PubMedCrossRef

19.

Peng H, Sohara Y, Moats RA, Nelson MD Jr, Groshen SG, Ye W, Reynolds CP, DeClerck YA (2007) The activity of zoledronic acid on neuroblastoma bone metastasis involves inhibition of osteoclasts and tumor cell survival and proliferation. Cancer Res 67:9346–9355PubMedCrossRef

20.

Poretti A, Grotzer MA (2012) Neuroblastoma with spinal cord compression: is there an emergency treatment of choice? Dev Med Child Neurol 54:297–298PubMedCrossRef

21.

Roodman GD (2004) Mechanisms of bone metastasis. N Engl J Med 351:195–196CrossRef

22.

Sartelet H, Durrieu L, Fontaine F, Nyalendo C, Haddad E (2012) Description of a new xenograft model of metastatic neuroblastoma using NOD/SCID/Il2rg null (NSG) mice. In Vivo 26:19–29PubMed

23.

Sharp SE, Gelfand MJ, Shulkin BL (2011) Pediatrics: diagnosis of neuroblastoma. Semin Nucl Med 41:345–353PubMedCrossRef

24.

Sohara Y, Shimada H, DeClerck YA (2005) Mechanisms of bone invasion and metastasis in human neuroblastoma. Cancer Lett 228:203–209PubMedCrossRef

25.

Sohara Y, Shimada H, Scadeng M, Pollack H, Yamada S, Ye W, Reynolds CP, DeClerck YA (2003) Lytic bone lesions in human neuroblastoma xenograft involve osteoclast recruitment and are inhibited by bisphosphonate. Cancer Res 63:3026–3031PubMed

26.

Sorrentino S, Rosanda C, Parodi S, Rita Gigliotti A, Pasino M, Defferrari R, Paolo Tonini G, De Bernardi B (2012) Cyto-morphologic evaluation of bone marrow in infants with disseminated neuroblastoma. J Pediatr Hematol Oncol 34:154–158PubMed

27.

Sun W, Modak S (2012) Emerging treatment options for the treatment of neuroblastoma: potential role of perifosine. Onco Targets Ther 5:21–29PubMed

28.

Suva LJ, Washam C, Nicholas RW, Griffin RJ (2011) Bone metastasis: mechanisms and therapeutic opportunities. Nat Rev Endocrinol 7:208–218PubMedCrossRef

29.

Ishola TA, Chung DH (2007) Neuroblastoma. Surg Oncol 16:149–156PubMedCrossRef

30.

van Golen CM, Schwab TS, Kim B, Soules ME, Su Oh S, Fung K, van Golen KL, Feldman EL (2006) Insulin-like growth factor-I receptor expression regulates neuroblastoma metastasis to bone. Cancer Res 66:6570–6578PubMedCrossRef

31.

Yang S, Zheng J, Ma Y, Zhu H, Xu T, Dong K, Xiao X (2012) Oct4 and Sox2 are overexpressed in human neuroblastoma and inhibited by chemotherapy. Oncol Rep 28:186–192PubMed

32.

Zhang L, Yeger H, Das B, Irwin MS, Baruchel S (2007) Tissue microenvironment modulates CXCR4 expression and tumor metastasis in neuroblastoma. Neoplasia 9:36–46PubMedCrossRef

Title: Establishment and characterization of xenograft models of human neuroblastoma bone metastasis
Authors: Hongyu Zhao
Weisong Cai
Shuai Li
Zuke Da
Hanxue Sun
Liang Ma
Yaoxin Lin
Debao Zhi
Publication date: 01-12-2012
Publisher: Springer-Verlag
Published in: Child's Nervous System / Issue 12/2012
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI: https://doi.org/10.1007/s00381-012-1909-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Establishment and characterization of xenograft models of human neuroblastoma bone metastasis

Abstract

Objects

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objects

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 12/2012

Cranioplasty in medieval Persia and the potential spread of this knowledge to Europe

Intracranial clear cell meningioma in two children with blood relations: two case reports and literature review

Iatrogenic intracranial aneurysms in childhood: case-based update

Microsurgical outlet restoration in isolated fourth ventricular hydrocephalus: a single-institutional experience

An unusual case of primary central nervous system germinoma with meningeal dissemination

Spinal cord ependymomas in children and adolescents