Focused microarray analysis of glyco-gene expression in human glioblastomas.
Altered glycosylation has been linked to cancer cell metastasis and invasivity. We have previously shown that expressing a specific sialyltransferase gene in gliomas inhibited tumor formation, in vivo. In order to identify other "glyco-gene" targets with therapeutic potential, focused 45-mer oligonucleotide microarrays were constructed containing all of the cloned human glyco-genes. Gene expression profiles of normal human brain and malignant gliomas were compared and microarray datasets analyzed using significance analysis of microarrays algorithms. There were 11 genes more highly expressed in gliomas compared to normal brain and 25 genes more highly expressed in normal brain compared to gliomas. Among the most noteworthy were high levels of MAN2A2 and ST6GalNAcV in normal brain tissue and high levels of POFUT1 and CHI3L1 in the gliomas, all changes corroborated by qRT-PCR. Historically, identification of changes in tumor-associated glycoconjugate expression was obtained by measuring individual enzyme activities or structural changes of specific molecules. With microarray technology, it is possible to measure all of genes associated with glycoconjugate biosynthesis and degradation simultaneously. Our data demonstrate that there are many significant and novel differences in glyco-gene expression that represent potential targets for the development of therapeutics for the treatment of brain tumors.
Kroes
Roger A
RA
Falk Center for Molecular Therapeutics, Department of Biomedical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, Illinois 60201, USA.
Dawson
Glyn
G
Moskal
Joseph R
JR
D000328:Adult; D000368:Aged; D000465:Algorithms; D001932:Brain Neoplasms / Q000235:genetics / Q000503:physiopathology*; D002241:Carbohydrates / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005909:Glioblastoma / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods
D002241:Carbohydrates