A. Rebbaa et al., Expression of bisecting GlcNAc in pediatric brain tumors and its association with tumor cell response to vinblastine, CLIN CANC R, 5(11), 1999, pp. 3661-3668
Increased expression of the bisecting GlcNAc has been correlated with tumor
progression in several experimental tumor models. Its expression and funct
ion in brain tumors are, however, not yet known. In this study, we investig
ated 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 nor
mal brain tissue specimens. Our results showed that, whereas E-PHA staining
was undetectable in the normal brain tissue, pediatric brain tumor specime
ns exhibited different levels of reactivity, Lectin staining was particular
ly prominent in high-grade astrocytomas (73%) and ependymomas (72%), In ast
rocytomas, there was a positive correlation with the tumor grade, which sug
gests that the bisecting GlcNAc may be of particular interest as a tumor ma
rker for diagnosis and/or prognosis. By using a human glioma cell culture m
odel, we have found that treatment of these cells with E-PHA lectin enhance
s their sensitivity to vinblastine. E-PHA interacted directly with the drug
transporter P-glycoprotein and inhibited its drug efflux function. In a dr
ug-resistant glioma cell line transfected with the mdr1 gene, drug resistan
ce 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.