N-Cadherin in Neuroblastoma Disease: Expression and Clinical Significance

被引:40
作者
Lammens, Tim [1 ]
Swerts, Katrien [1 ]
Derycke, Lara [2 ]
De Craemer, Annemie [1 ]
De Brouwer, Sara [3 ]
De Preter, Katleen [3 ]
Van Roy, Nadine [3 ]
Vandesompele, Jo [3 ]
Speleman, Frank [3 ]
Philippe, Jan [4 ]
Benoit, Yves [1 ]
Beiske, Klaus [5 ]
Bracke, Marc [2 ]
Laureys, Genevieve [1 ]
机构
[1] Ghent Univ Hosp, Dept Pediat Hematol Oncol, Ghent, Belgium
[2] Ghent Univ Hosp, Dept Radiat Oncol & Expt Canc Res, Ghent, Belgium
[3] Ghent Univ Hosp, Ctr Med Genet, Ghent, Belgium
[4] Ghent Univ Hosp, Dept Clin Chem Microbiol & Immunol, Ghent, Belgium
[5] Univ Oslo, Rikshosp, Dept Pathol, N-0027 Oslo, Norway
来源
PLOS ONE | 2012年 / 7卷 / 02期
关键词
CELL-ADHESION; TUMOR PROGRESSION; METASTASIS; INVASION; SUPPRESSES; PEPTIDE; ADH-1; GENE; DIFFERENTIATION; OSTEOSARCOMA;
D O I
10.1371/journal.pone.0031206
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
One of the first and most important steps in the metastatic cascade is the loss of cell-cell and cell-matrix interactions. N-cadherin, a crucial mediator of homotypic and heterotypic cell-cell interactions, might play a central role in the metastasis of neuroblastoma (NB), a solid tumor of neuroectodermal origin. Using Reverse Transcription Quantitative PCR (RT-qPCR), Western blot, immunocytochemistry and Tissue MicroArrays (TMA) we demonstrate the expression of N-cadherin in neuroblastoma tumors and cell lines. All neuroblastic tumors (n = 356) and cell lines (n = 10) expressed various levels of the adhesion protein. The N-cadherin mRNA expression was significantly lower in tumor samples from patients suffering metastatic disease. Treatment of NB cell lines with the N-cadherin blocking peptide ADH-1 (Exherin, Adherex Technologies Inc.), strongly inhibited tumor cell proliferation in vitro by inducing apoptosis. Our results suggest that N-cadherin signaling may play a role in neuroblastoma disease, marking involvement of metastasis and determining neuroblastoma cell viability.
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页数:8
相关论文
共 41 条
  • [1] Reduced expression of plakoglobin correlates with adverse outcome in patients with neuroblastoma
    Amitay, R
    Nass, D
    Meitar, D
    Goldberg, I
    Davidson, B
    Trakhtenbrot, L
    Brok-Simoni, F
    Ben-Ze'ev, A
    Rechavi, G
    Kaufmann, Y
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2001, 159 (01) : 43 - 49
  • [2] Mechanisms of invasion and metastasis in human neuroblastoma
    Ara, Tasnim
    DeClerck, Yves A.
    [J]. CANCER AND METASTASIS REVIEWS, 2006, 25 (04) : 645 - 657
  • [3] Targeting N-cadherin enhances antitumor activity of cytotoxic therapies in melanoma treatment
    Augustine, Christina K.
    Yoshimoto, Yasunori
    Gupta, Mukur
    Zipfel, Patricia A.
    Selim, M. Angelica
    Febbo, Phillip
    Pendergast, Ann Marie
    Peters, William P.
    Tyler, Douglas S.
    [J]. CANCER RESEARCH, 2008, 68 (10) : 3777 - 3784
  • [4] A Phase 1 Study of Systemic ADH-1 in Combination With Melphalan via Isolated Limb Infusion in Patients With Locally Advanced In-Transit Malignant Melanoma
    Beasley, Georgia M.
    McMahon, Nicole
    Sanders, Gretchen
    Augustine, Christina K.
    Selim, Maria A.
    Peterson, Bercedis
    Norris, Robin
    Peters, William P.
    Ross, Merrick I.
    Tyler, Douglas S.
    [J]. CANCER, 2009, 115 (20) : 4766 - 4774
  • [5] Metastasis suppressor genes - From gene identification to protein function and regulation
    Berger, JC
    Vander Griend, DJ
    Robinson, VL
    Hickson, JA
    Rinker-Schaeffer, CW
    [J]. CANCER BIOLOGY & THERAPY, 2005, 4 (08) : 805 - 812
  • [6] Cadherins as novel targets for anti-cancer therapy
    Blaschuk, Orest W.
    Devemy, Emmanuelle
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 2009, 625 (1-3) : 195 - 198
  • [7] Brodeur G.M., 1993, Principles and practice of pediatric oncology, P739
  • [8] INTERNATIONAL CRITERIA FOR DIAGNOSIS, STAGING, AND RESPONSE TO TREATMENT IN PATIENTS WITH NEURO-BLASTOMA
    BRODEUR, GM
    SEEGER, RC
    BARRETT, A
    BERTHOLD, F
    CASTLEBERRY, RP
    DANGIO, G
    DEBERNARDI, B
    EVANS, AE
    FAVROT, M
    FREEMAN, AI
    HAASE, G
    HARTMANN, O
    HAYES, FA
    HELSON, L
    KEMSHEAD, J
    LAMPERT, F
    NINANE, J
    OHKAWA, H
    PHILIP, T
    PINKERTON, CR
    PRITCHARD, J
    SAWADA, T
    SIEGEL, S
    SMITH, EI
    TSUCHIDA, Y
    VOUTE, PA
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 1988, 6 (12) : 1874 - 1881
  • [9] Burden-gulley SM, 1999, PEPTIDES, V31, P842
  • [10] Cadherins and the tumour progression: is it all in a switch?
    Cavallaro, U
    Schaffhauser, B
    Christofori, G
    [J]. CANCER LETTERS, 2002, 176 (02) : 123 - 128