Constitutive expression of growth-related oncogene and its receptor in oligodendrogliomas

OBJECTIVE: Gliomas may result from transformation of glial precursor cells. In the developing rat central nervous system (CNS), a paracrine pathway in volving the cytokines growth-related oncogene (GRO1) and platelet-derived g rowth factor (PDGF) A chain closely regulates oligodendrocyte precursor cel l number. The purpose of the present study was to analyze whether abnormal expression and activity of the GRO1-PDGF pathway is present in human glioma s. METHODS: Tumor specimens were studied to compare the messenger ribonucleic acid with the protein expression of components of the GRO1-PDGF pathway. Ne utralizing antibodies were used in vitro to analyze whether the pathway con tributed to tumor cell proliferation. RESULTS: Immunohistochemistry demonstrated that all components of the GRO1- PDGF pathway (GRO1 protein, its receptor CXCR2, EDGE A chain, and its recep tor PDGF alphaR) were expressed by tumor cells in 6 (86%) of 7 of oligodend rogliomas as well as by 0 of 4 diffuse astrocytomas (World Health Organizat ion Grades II and III) and 2 (18%) of 11 glioblastomas. Analysis by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent as say showed CXCR2 messenger ribonucleic acid and GRO1 protein expression wer e present in oligodendrogliomas. Functional analyses with neutralizing anti bodies limited bromodeoxyuridine incorporation in vitro by oligodendrogliom a tumor cells, demonstrating a requirement for the GRO1-PDGF pathway in the proliferation of these cells. CONCLUSION: The GRO1-PDGF pathway was primarily expressed and functional in oligodendrogliomas. The tightly controlled paracrine pathway that regulate s oligodendrocyte precursor proliferation in the developing rodent CNS was constitutively active in most oligodendrogliomas in the present study. The presence of this aberrantly functioning oncogenic pathway in a subset of pr imary CNS tumors opens new avenues to glioma treatment that are based direc tly on the biology of the proliferative glial cell type, a novel strategy f or primary CNS tumor therapy.