Rhabdomyosarcomas utilize developmental, myogenic growth factors for disease advantage: A report from the Children's Oncology Group

被引:49
作者
Blandford, MC
Barr, FG
Lynch, JC
Randall, RL
Qualman, SJ
Keller, C
机构
[1] Univ Utah, Dept Pediat, Div Pediat Hematol Oncol, Salt Lake City, UT USA
[2] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
[3] Univ Nebraska Med Ctr, Dept Prevent & Societal Med, Omaha, NE 68198 USA
[4] Univ Utah, Huntsman Canc Inst, Sarcoma Serv, Dept Orthoped, Salt Lake City, UT USA
[5] Columbus Childrens Hosp, Dept Lab Med, Columbus, OH USA
关键词
insulin-like growth factor; rnetastasis; myogenesis; platelet-derived growth factor; progression; rhabdomyosarcoma;
D O I
10.1002/pbc.20466
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background. Unresectable or metastatic disease represents the greatest obstacle to cure for children with rhabdomyosarcoma. in this study we sought to identify gene expression signatures of advanced stage and progressive disease. Procedure. Using oligonucleotide gene expression analysis for a focused set of 60 genes, we analyzed the myogenic expression profiles of 89 rhabdomyosarcomas from the Intergroup Rhabdomyosarcoma Study-IV. Results. While the expression profile of rhabdomyosarcomas closely paralleled gene expression profiles of normal embryonic myogenic progenitors, growth factors were most closely associated with disease progression. Specifically, we identified platelet-derived growth factor (PDGF) receptors and insulin-like growth factor as strongly correlated with decreased failure-free survival. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) of an independent data set suggested that autocrine growth signaling, if present, is not regulated in a simple manner at the transcriptional level. Conclusions. increased transcriptional levels of PDGF receptors and insulin-like growth factor are associated with decreased survival in rhabdomyosarcomas. Dual blockade of these growth-factor-signaling pathways may be a valuable strategy in preclinical therapeutic Studies.
引用
收藏
页码:329 / 338
页数:10
相关论文
共 49 条
[21]  
Hachitanda Y, 1998, MODERN PATHOL, V11, P1222
[22]   Patched target Igf2 is indispensable for the formation of medulloblastoma and rhabdomyosarcoma [J].
Hahn, H ;
Wojnowski, L ;
Specht, K ;
Kappler, R ;
Calzada-Wack, J ;
Potter, D ;
Zimmer, A ;
Müller, U ;
Samson, E ;
Quintanilla-Martinez, L ;
Zimmer, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (37) :28341-28344
[23]   Rhabdomyosarcomas and radiation hypersensitivity in a mouse model of Gorlin syndrome [J].
Hahn, H ;
Wojnowski, L ;
Zimmer, AM ;
Hall, J ;
Miller, G ;
Zimmer, A .
NATURE MEDICINE, 1998, 4 (05) :619-622
[24]   A single amino acid substitution in a WW-like domain of diverse members of the PDGF receptor subfamily of tyrosine kinases causes constitutive receptor activation [J].
Irusta, PM ;
DiMaio, D .
EMBO JOURNAL, 1998, 17 (23) :6912-6923
[25]   Alveolar rhabdomyosarcomas in conditional Pax3:Fkhr mice:: cooperativity of Ink4a/ARF and Trp53 loss of function [J].
Keller, C ;
Arenkiel, BR ;
Coffin, CM ;
El-Bardeesy, N ;
DePinho, RA ;
Capecchi, MR .
GENES & DEVELOPMENT, 2004, 18 (21) :2614-2626
[26]   Pax3:Fkhr interferes with embryonic Pax3 and Pax7 function:: implications for alveolar rhabdomyosarcoma cell of origin [J].
Keller, C ;
Hansen, MS ;
Coffin, CM ;
Capecchi, MR .
GENES & DEVELOPMENT, 2004, 18 (21) :2608-2613
[27]  
KHATIB ZA, 1993, CANCER RES, V53, P5535
[28]   BMP5 AND THE MOLECULAR, SKELETAL, AND SOFT-TISSUE ALTERATIONS IN SHORT EAR MICE [J].
KING, JA ;
MARKER, PC ;
SEUNG, KJ ;
KINGSLEY, DM .
DEVELOPMENTAL BIOLOGY, 1994, 166 (01) :112-122
[29]   LOSS OF THE IMPRINTED IGF2/CATION-INDEPENDENT MANNOSE 6-PHOSPHATE RECEPTOR RESULTS IN FETAL OVERGROWTH AND PERINATAL LETHALITY [J].
LAU, MMH ;
STEWART, CEH ;
LIU, ZY ;
BHATT, H ;
ROTWEIN, P ;
STEWART, CL .
GENES & DEVELOPMENT, 1994, 8 (24) :2953-2963
[30]   The insulin-like growth factor system and cancer [J].
LeRoith, D ;
Roberts, CT .
CANCER LETTERS, 2003, 195 (02) :127-137