Endothelins may modulate invasion and proliferation of Ewing's sarcoma and neuroblastoma.
Tumours of the Ewing's sarcoma (ES) family and neuroblastoma (NBL) were examined by reverse transcriptase-PCR for expression of mRNA for endothelin (ET) receptors ET-A and ET-B, and the ligands ET-1, ET-2 and ET-3. The effect of ET-1, ET-3, an ET-1-neutralizing antibody and ET-A receptor antagonist BQ-123 on cell proliferation was examined using an ELISA. Loss of ET-B receptor mRNA occurred in 57% of ES and 42% of NBL tumours. This appeared to be associated with the presence of metastatic disease and disease progression. ET-A receptor mRNA was expressed in all ES and 85% of NBL tumours, and in all ES and NBL cell lines examined. All ET ligands were detected in NBL cell lines, but only ET-1 and ET-2 were expressed in ES cell lines. Treatment of ES and NBL cells with ET-1 increased proliferation, but ET-3 had no effect. Incubation of ES and NBL cells with an ET-1-neutralizing antibody or BQ-123 decreased proliferation. The ET-3 ligand and ET-B receptor may be associated with migration and metastasis of ES and NBL, whereas ET-1 (acting through the ET-A receptor) may regulate their proliferation.
Division of Cancer Medicine, Cancer Research U.K. Clinical Centre, St James's University Hospital, Leeds LS9 7TF, U.K. csjpab@cancermed.ledds.ac.uk
Paul
P
Berry
Susan
S
Burchill
D019332:Endothelin-1 / Q000235:genetics; D019333:Endothelin-2 / Q000235:genetics; D019334:Endothelin-3 / Q000235:genetics; D016232:Endothelins / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009447:Neuroblastoma / Q000737:chemistry* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis*; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012512:Sarcoma, Ewing / Q000737:chemistry* / Q000473:pathology; D014407:Tumor Cells, Cultured
D019332:Endothelin-1; D019333:Endothelin-2; D019334:Endothelin-3; D016232:Endothelins; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin