Heparanase, TrkC and p75NTR: their functional involvement in human medulloblastoma cell invasion.
Medulloblastoma is the most common malignant childhood brain tumor. Although some previous reports have shown up to a 70% 5-year survival for some of these patients, it is at the cost of significant long-term treatment-related morbidity. The cellular mechanisms leading to metastatic disease in medulloblastoma are mainly unknown. For the first time, we demonstrate the differential expression of heparanase in medulloblastomas and how these differences at the mRNA and protein levels affect the activity and invasive properties of three newly developed cell lines. Furthermore, heparanase expression was confirmed in 7 (88%) of 8 medulloblastoma clinical samples by immunohistochemical staining. Heparanase was found to be localized in the cytoplasm and nucleus. Quantitative polymerase chain reaction revealed a negative correlation between heparanase and TrkC (which is associated with a favorable clinical outcome). The activation of TrkC or TrkC/p75NTR by NT-3 affected heparanase activity and cell-invasive properties of medulloblastoma cells in vitro. Taken together, our data extend the body of evidence that invasion and expression/functionality of heparanase, in a context linked to TrkC and p75NTR, may play critical roles in the disease progression of medulloblastoma.
Sinnappah-Kang
Neeta D
ND
Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University-Baton Rouge, Baton Rouge, LA 70803, USA.
Kaiser
Adam J
AJ
Blust
Bryan E
BE
Mrak
Robert E
RE
Marchetti
Dario
D
D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness; D020933:Neurotrophin 3 / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor; D020812:Receptor, trkC / Q000235:genetics / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099175:Heparanase
D014408:Biomarkers, Tumor; D005966:Glucuronidase; D020933:Neurotrophin 3; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D020812:Receptor, trkC; D017475:Receptors, Nerve Growth Factor; D000099175:Heparanase