Altered expression of natively glycosylated α dystroglycan in pediatric solid tumors

SummaryAltered glycosylation and/or expression of dystroglycan have been reported in forms of congenital muscular dystrophy as well as in cancers of the breast, colon, and oral epithelium. To date, however, there has been no study of the expression of dystroglycan in pediatric solid tumors. Using a combination of immunostaining on tissue microarrays and immunoblotting of snap-frozen unfixed tissues, we demonstrate a significant reduction in native α dystroglycan expression in pediatric alveolar rhabdomyosarcoma (RMS), embryonal RMS, neuroblastoma (NBL), and medulloblastoma, whereas expression of β dystroglycan, which is cotranslated with α dystroglycan, is largely unchanged. Loss of native α dystroglycan expression was significantly more pronounced in stage 4 NBL than in pooled samples of stage 1 and stage 2 NBL, suggesting that loss of native α dystroglycan expression increases with advancing tumor stage. Neuroblastoma and RMS samples with reduced expression of native α dystroglycan also showed reduced laminin binding in laminin overlay experiments. Expression of natively glycosylated α dystroglycan was not altered in several other pediatric tumor types when compared with appropriate normal tissue controls. These data provide the first evidence that α dystroglycan glycosylation and laminin binding to α dystroglycan are altered in certain pediatric solid tumors and suggest that aberrant dystroglycan glycosylation may contribute to tumor cell biology in patients with RMS, medulloblastoma, and NBL.