Characterization of a pineal region malignant rhabdoid tumor. Towards understanding brain tumor cell invasion.
The malignant rhabdoid tumor (MRT) of the central nervous system is a highly aggressive neoplasm of early infancy which is characterized by brain invasion and widespread dissemination along cerebrospinal fluid pathways. As the process of tumor invasion is mediated in part by the elaboration of proteases and protease inhibitors by tumor cells, we sought to determine the expression of the type-IV collagenases and their inhibitors (tissue inhibitors of metalloproteases, TIMPs) in an MRT from the pineal region of a 9-month-old male. In addition, as only a few reports exist concerning the cytogenetic abnormalities in MRTs, the cytogenetic features of this MRT were examined. When placed into tissue culture, the MRT grew vigorously in early passages. The cytogenetic analysis of the cells in passage one revealed a near diploid karyotype with some metaphases demonstrating monosomy 22. Northern analysis of type-IV collagenase transcripts revealed that the MRT expressed the highest levels of the 72- and 92-kD type-IV collagenase transcripts of any pediatric brain tumor examined. However, the MRT did not express any significant amounts of the TIMP-1 or TIMP-2 transcripts. By in situ hybridization analysis, the MRT demonstrated marked intratumoral expression of the type-IV collagenase but not TIMP transcripts. The results from this study suggest that this particular MRT may be a highly invasive brain tumor, at least in part on the basis of overexpression of the type-IV collagenases relative to the TIMPs.
Muller
M
M
Brain Tumor Research Laboratory, Hospital for Sick Children, University of Toronto, Ont., Canada.
Hubbard
S L
SL
Fukuyama
K
K
Dirks
P
P
Matsuzawa
K
K
Rutka
J T
JT
D014408:Biomarkers, Tumor / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D002869:Chromosome Aberrations; D002892:Chromosomes, Human, Pair 22; D017364:Collagenases / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness; D010870:Pineal Gland / Q000473:pathology* / Q000601:surgery; D011506:Proteins / Q000235:genetics; D018335:Rhabdoid Tumor / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases; D014158:Transcription, Genetic
D014408:Biomarkers, Tumor; D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D011506:Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D017364:Collagenases