Metastatic human rhabdomyosarcoma: molecular, cellular and cytogenetic analysis of a novel cellular model.
A new human metastatic rhabdomyosarcoma (RMS) model was established and analyzed for a number of biologic, cytogenetic and molecular parameters. Consistent with previous studies, the metastatic capacity of different RMS cell variants did not correlate with their tumorigenic or proliferative capacities. Interestingly, a highly metastatic variant was diploid, while a nonmetastatic variant was tetraploid, which parallels previous clinical observations. Genes whose expression had been found to be associated with either low- or high-metastatic capacity in carcinoma or melanoma did not show a similar association with different metastatic variants of RMS, derived from a mesenchymal tumor. We also found, in transient reporter gene assays, that several promoters had higher transcriptional activity in highly metastatic than in nonmetastatic RMS cell variants. This novel human RMS metastatic model may be instrumental for a better understanding of the regulatory pathways that control the metastatic phenotype of tumors of mesenchymal origin.
Kalebic
T
T
Molecular Oncology Section, National Cancer Institute, Rockville Pike, Bethesda, Md 20892, USA.
Judde
J G
JG
Velez-Yanguas
M
M
Knutsen
T
T
Helman
L J
LJ
D000818:Animals; D002455:Cell Division; D004171:Diploidy; D018093:Gelatinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism; D009368:Neoplasm Transplantation; D011123:Polyploidy; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012208:Rhabdomyosarcoma / Q000235:genetics / Q000473:pathology*; D014162:Transfection
D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2