Expression of syndecans, a heparan sulfate proteoglycan, in malignant gliomas: participation of nuclear factor-kappaB in upregulation of syndecan-1 expression.
Invasion of tumor cells into the surrounding normal brain tissues is a prominent feature of malignant gliomas. Malignant glioma cells secrete thrombospondin-1 which participates in the motility of glioma cells and binds cell surface heparan sulfate proteoglycan. To clarify the invasion mechanism of tumor cells, expression of the syndecans (syndecan-1, -2, -3, and -4), a major cell surface heparan sulfate proteoglycan family, was analyzed in malignant gliomas. Involvement of nuclear factor-kappaB (NF-kappaB) on syndecan-1 expression was also investigated. Using reverse transcription-PCR, the authors analyzed the expression of syndecan-1, -2, -3, and -4 in 10 malignant glioma cell lines, 2 glioblastoma specimens, and 2 normal brain specimens. All malignant glioma cell lines and glioblastoma specimens expressed all types of syndecan mRNA, except in one glioma cell line that lacked syndecan-3 expression. On the other hand, normal brain specimens expressed syndecan-2, -3, and -4 mRNA, but did not syndecan-1 mRNA. Syndecan-1 protein was localized in the cell surface of all malignant glioma cell lines by flow cytometry. Various levels of active nuclear factor-kappa B (NF-kappaB) was detected in all malignant glioma cell lines using immunoblotting. The expression of active NF-kappaB and syndecan-1 increased in U251 glioma cells after tumor necrosis factor-alpha or interleukin-1beta treatment, which can activate NF-kappaB. The amplification of active NF-kappaB and syndecan-1 by tumor necrosis factor-alpha or interleukin-1beta was suppressed by an inhibitor of NF-kappaB activation (emodin). Emodin also downregulated the expression of syndecan-1 mRNA in U251 cells. These results indicate that malignant glioma cells express all types of syndecans and suggest that NF-kappaB participates in the upregulation of the syndecan-1 expression at the transcriptional level, and increased expression of syndecan-1 could associate with extracellular matrices including thrombospondin-1.
Watanabe
Arata
A
Department of Neurosurgery, University of Yamanashi, Faculty of Medicine, 409 3898, Nakakoma-gun, Yamanashi, Japan.
Mabuchi
Tadashi
T
Satoh
Eiji
E
Furuya
Koro
K
Zhang
Lei
L
Maeda
Shuichiro
S
Naganuma
Hirofumi
H
D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002540:Cerebral Cortex / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008233:Lymphotoxin-alpha / Q000502:physiology; D008562:Membrane Glycoproteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011509:Proteoglycans / Q000145:classification / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D053668:Syndecan-1; D053669:Syndecan-2; D053670:Syndecan-3; D053671:Syndecan-4; D053667:Syndecans; D019700:Thrombospondin 1 / Q000378:metabolism
D016326:Extracellular Matrix Proteins; D019812:Heparan Sulfate Proteoglycans; D008233:Lymphotoxin-alpha; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011509:Proteoglycans; D012333:RNA, Messenger; C508241:SDC1 protein, human; C508245:SDC2 protein, human; C508301:SDC3 protein, human; C508304:SDC4 protein, human; D053668:Syndecan-1; D053670:Syndecan-3; D053671:Syndecan-4; D053667:Syndecans; D019700:Thrombospondin 1; D016222:Fibroblast Growth Factor 2; D053669:Syndecan-2