The MET receptor tyrosine kinase contributes to invasive tumour growth in rhabdomyosarcomas.
The receptor tyrosine kinase MET and its ligand hepatocyte growth factor (HGF), have been implicated in the genesis of the paediatric tumour rhabdomyosarcoma (RMS). Addition of exogenous HGF to RH30 RMS cells enhanced non-chemotactic migration. Stable transfection of dominant negative MET into RH30 cells attenuated Matrigel invasion and in vivo tumour growth. To assess the role of a putative HGF-MET pathway in human RMS, we measured their expression in a panel of 68 human primary tumours. All tumours expressed MET but with a three orders of magnitude variation of expression and 62% of tumours co-expressed HGF. In contrast with other tumour types, neither high-MET expression nor HGF/MET coexpression correlated with metastatic disease. In a microarray screen, we identified CCN1 as being 7.8-fold up regulated following addition of HGF to RH30 cells and in RMS tumours, CCN1 expression correlated with HGF expression. Surprisingly, we identified MET as a consistent feature of embryonal and not alveolar RMS.
Rees
Helen
H
Unit of Molecular Haematology and Cancer Biology, Institute of Child Health, London, WC1N 1EH, UK.
Williamson
Daniel
D
Papanastasiou
Antigoni
A
Jina
Nipurna
N
Nabarro
Steven
S
Shipley
Janet
J
Anderson
John
J
D000818:Animals; D045744:Cell Line, Tumor; D003094:Collagen; D004338:Drug Combinations; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007797:Laminin; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D009361:Neoplasm Invasiveness; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000502:physiology; D011509:Proteoglycans; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism / Q000502:physiology*; D018232:Rhabdomyosarcoma, Alveolar / Q000503:physiopathology*; D015854:Up-Regulation
D004338:Drug Combinations; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D007797:Laminin; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D011509:Proteoglycans; C059485:matrigel; D017228:Hepatocyte Growth Factor; D003094:Collagen; D019859:Proto-Oncogene Proteins c-met