Expression of bisecting GlcNAc in pediatric brain tumors and its association with tumor cell response to vinblastine.
Increased expression of the bisecting GlcNAc has been correlated with tumor progression in several experimental tumor models. Its expression and function in brain tumors are, however, not yet known. In this study, we investigated expression of the bisecting GlcNAc structure in a series of pediatric brain tumors and its relationship to tumor response to vinblastine. A plant lectin (E-PHA) that recognizes the bisecting GlcNAc structure was used for detection of this molecule in a total of 90 pediatric brain tumors and normal brain tissue specimens. Our results showed that, whereas E-PHA staining was undetectable in the normal brain tissue, pediatric brain tumor specimens exhibited different levels of reactivity. Lectin staining was particularly prominent in high-grade astrocytomas (73%) and ependymomas (72%). In astrocytomas, there was a positive correlation with the tumor grade, which suggests that the bisecting GlcNAc may be of particular interest as a tumor marker for diagnosis and/or prognosis. By using a human glioma cell culture model, we have found that treatment of these cells with E-PHA lectin enhances their sensitivity to vinblastine. E-PHA interacted directly with the drug transporter P-glycoprotein and inhibited its drug efflux function. In a drug-resistant glioma cell line transfected with the mdr1 gene, drug resistance was reversed by E-PHA. Our findings indicate that: (a) expression of the bisecting GlcNAc in pediatric brain tumors may have a potential relevance as a tumor marker; and (b) glioma response to chemotherapy may be modulated through the bisecting GlcNAc.
Rebbaa
A
A
Cancer Biology and Chemotherapy Program, Children's Memorial Hospital, Chicago, Illinois 60614, USA.
Chou
P M
PM
Vucic
I
I
Mirkin
B L
BL
Tomita
T
T
Bremer
E G
EG
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000117:Acetylglucosamine / Q000032:analysis / Q000378:metabolism*; D001254:Astrocytoma / Q000473:pathology; D001932:Brain Neoplasms / Q000473:pathology*; D002240:Carbohydrate Sequence; D002455:Cell Division / Q000187:drug effects; D002528:Cerebellar Neoplasms / Q000473:pathology; D002540:Cerebral Cortex / Q000166:cytology* / Q000473:pathology; D004806:Ependymoma / Q000473:pathology; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D006031:Glycosylation; D006801:Humans; D037102:Lectins; D008527:Medulloblastoma / Q000473:pathology; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000096:biosynthesis / Q000737:chemistry; D010835:Phytohemagglutinins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000633:toxicity*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D037102:Lectins; D009844:Oligosaccharides; D010835:Phytohemagglutinins; C067494:erythroagglutinating phytohemagglutinin; D014747:Vinblastine; D000117:Acetylglucosamine