Large-scale molecular comparison Schwann cells to malignant peripheral nerve sheath tumor cell lines and tissues

被引:152
作者
Miller, SJ
Rangwala, F
Williams, J
Ackerman, P
Kong, S
Jegga, AG
Kaiser, S
Aronow, BJ
Frahm, S
Kluwe, L
Mautner, V
Upadhyaya, M
Muir, D
Wallace, M
Hagen, J
Quelle, DE
Watson, MA
Perry, A
Gutmann, DH
Ratner, N
机构
[1] Univ Cincinnati, Childrens Hosp,Coll Med, Ctr Med,Res Fdn, Div Expt Hematol, Cincinnati, OH 45229 USA
[2] Univ Cincinnati, Childrens Hosp,Coll Med, Ctr Med,Res Fdn, Div Biomed Informat, Cincinnati, OH 45229 USA
[3] Univ Hamburg, Clin Eppendorf, Dept Neurosurg, Hamburg, Germany
[4] Univ Wales Coll Med, Inst Med Genet, Cardiff, Wales
[5] Univ Florida, Dept Pediat Neurol, Gainesville, FL 32611 USA
[6] Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL 32611 USA
[7] Univ Iowa, Coll Med, Dept Pharmacol, Iowa City, IA 52242 USA
[8] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA
[9] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63130 USA
关键词
D O I
10.1158/0008-5472.CAN-05-3330
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Malignant peripheral nerve sheath tumors (MPNST) are highly invasive soft tissue sarcomas that arise within the peripheral nerve and frequently metastasize. To identify molecular events contributing to malignant transformation in peripheral nerve, we compared eight cell lines derived from MPNSTs and seven normal human Schwann cell samples. We found that MPNST lines are heterogeneous in their in vitro growth rates and exhibit diverse alterations in expression of pRb, p53, p14(Arf), and p16(INK4a) proteins. All MPNST cell lines express the epidermal growth factor receptor and lack S100 beta protein. Global gene expression profiling using Affymetrix oligonucleotide microarrays identified a 159-gene molecular signature distinguishing MPNST cell lines from normal Schwann cells, which was validated in Affymetrix microarray data generated from 45 primary MPNSTs. Expression of Schwann cell differentiation markers (SOX10, CAP, PMP22, and NGFR) was down-regulated in MPNSTs whereas neural crest stem cell markers, SOX9 and TWIST1, were overexpressed in MPNSTs. Previous studies have implicated TWIST1 in apoptosis inhibition, resistance to chemotherapy, and metastasis. Reducing TWIST1 expression in MPNST cells using small interfering RNA did not affect apoptosis or chemoresistance but inhibited cell chemotaxis. Our results highlight the use of gene expression profiling in identifying genes and molecular pathways that are potential biomarkers and/or therapeutic targets for treatment of MPNST and support the use of the MPNST cell lines as a primary analytic tool.
引用
收藏
页码:2584 / 2591
页数:8
相关论文
共 55 条
  • [1] Badache A, 1998, J CELL PHYSIOL, V177, P334, DOI 10.1002/(SICI)1097-4652(199811)177:2<334::AID-JCP15>3.0.CO
  • [2] 2-9
  • [3] Berner JM, 1999, GENE CHROMOSOME CANC, V26, P151, DOI 10.1002/(SICI)1098-2264(199910)26:2<151::AID-GCC7>3.3.CO
  • [4] 2-1
  • [5] Rb and TP53 pathway alterations in sporadic and NF1-related malignant peripheral nerve sheath tumors
    Birindelli, S
    Perrone, F
    Oggionni, M
    Lavarino, C
    Pasini, B
    Vergani, B
    Ranzani, GN
    Pierotti, MA
    Pilotti, S
    [J]. LABORATORY INVESTIGATION, 2001, 81 (06) : 833 - 844
  • [6] A Twist in fate: evolutionary comparison of Twist structure and function
    Castanon, I
    Baylies, MK
    [J]. GENE, 2002, 287 (1-2) : 11 - 22
  • [7] Neural crest development is regulated by the transcription factor Sox9
    Cheung, M
    Briscoe, J
    [J]. DEVELOPMENT, 2003, 130 (23): : 5681 - 5693
  • [8] RADIOSENSITIVITY INVITRO OF HUMAN SOFT-TISSUE SARCOMA CELL-LINES AND SKIN FIBROBLASTS DERIVED FROM THE SAME PATIENTS
    DAHLBERG, WK
    LITTLE, JB
    FLETCHER, JA
    SUIT, HD
    OKUNIEFF, P
    [J]. INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 1993, 63 (02) : 191 - 198
  • [9] Epidermal growth factor receptor expression in. neurofibromatosis type 1-related tumors and NF1 animal models
    DeClue, JE
    Heffelfinger, S
    Benvenuto, G
    Ling, B
    Li, SW
    Rui, W
    Vass, WC
    Viskochil, D
    Ratner, N
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2000, 105 (09) : 1233 - 1241
  • [10] Ferner RE, 2002, CANCER RES, V62, P1573