Platelet-derived growth factor-B and -C and active alpha-receptors in medulloblastoma cells.
The malignant childhood brain tumor medulloblastoma belongs to the group of primitive neuroectodermal tumours (PNETs). Medulloblastomas are thought to arise from remnants of the transient external germinal layer in the cerebellum. Proliferation, differentiation, and motility of cells in the central nervous system are regulated by growth factors, e.g., platelet-derived growth factor (PDGF). Recently, it was shown that higher level of PDGF alpha-receptor expression is characteristic of metastatic medulloblastomas. We have investigated five medulloblastoma/PNET cell lines and found that the PDGF alpha-receptor is actively signalling in most of them, an activity most likely driven by endogenously produced PDGF-C. PDGF-C is normally present in cells of the developing external germinal layer and our results are consistent with the idea that medulloblastomas are derived from such cells undergoing early neuronal differentiation. Moreover, the expression of PDGF and its receptors was associated with neuronal characteristics, but not with high levels of c-myc expression in the medullablastoma cells.
Andrae
Johanna
J
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
Molander
Catrin
C
Smits
Anja
A
Funa
Keiko
K
Nistér
Monica
M
D002454:Cell Differentiation; D002478:Cells, Cultured; D002528:Cerebellar Neoplasms / Q000235:genetics / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008222:Lymphokines; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D016271:Proto-Oncogene Proteins c-myc; D020574:Proto-Oncogene Proteins c-sis; D012334:RNA, Neoplasm; C411423:platelet-derived growth factor C; D020796:Receptor, Platelet-Derived Growth Factor alpha