Overexpression of murine Pax3 increases NCAM polysialylation in a human medulloblastoma cell line

Polysialic acid (PSA) is a developmentally regulated carbohydrate found pri marily on neural cell adhesion molecules (NCAM) in embryonic tissues. The m ajority of NCAM in adult tissues lacks this unique carbohydrate, but polysi alylated NCAM (PSA-NCAM) is present in adult brain regions where neural reg eneration persists and in some pediatric brain tumors such as medulloblasto ma, which show greater propensity for leptomeningeal spread. Pax3, a develo pmentally regulated paired homeodomain transcription factor, is thought to be involved in the regulation of neural cell adhesion molecules. Overexpres sion of murine Pax3 into a human medulloblastoma cell line (DAOY) resulted in an increase in NCAM polysialylation and a 2-4-fold increase in alpha 2,8 -polysialyltransferase type II mRNA levels. No difference was observed in a lpha 2,8-polysialyltransferase type n7 message. The addition of PSA to NCAM changed the adhesive behavior of these Pax3 transfectants. Transfectants e xpressing high PSA-NCAM show much less NCAM-dependent aggregation than thos e with less PSA-NCAM. In addition, Pax3 transfectants having high PSA-NCAM show heterophilic adhesion involving polysialic acid to heparan sulfate pro teoglycan and agrin. These observations suggest that a developmentally regu lated transcription factor, Pax3, could affect NCAM polysialylation and sub sequently cell cell and cell-substratum interaction.