POLYSIALIC ACID ON THE NEURAL CELL-ADHESION MOLECULE CORRELATES WITH EXPRESSION OF POLYSIALYLTRANSFERASES AND PROMOTES NEUROBLASTOMA CELL-GROWTH

Neuroblastomas and cell lines derived from these tumors bear the oncod evelopmental antigen polysialic acid (PSA) bound to the neural cell ad hesion molecule, Polysialylation of neural cell adhesion molecule can be achieved by two different polysialyltransferases, ST8SiaII and ST8S iaIV, This study was undertaken to investigate the pattern of polysial yltransferases expressed in the human neuroblastoma cell line SH-SY5Y. Reverse transcription-PCR showed simultaneous expression of the two e nzymes, and in situ hybridization demonstrated that the polysialyltran sferase mRNA expression parallels immunoreactivity with the PSA-specif ic monoclonal antibody 735, After retinoic acid-induced differentiatio n, only the PSA-positive, neuron-like cell type gave clear signals for ST8SiaII and ST8SiaIV in in situ hybridization, whereas both signals were drastically reduced in the weakly PSA-positive substrate adherent phenotype, Like the SH-SY5Y cells, a primary, PSA-positive neuroblast oma specimen revealed expression of the two polysialyltransferases. To investigate the role of PSA for cell growth and differentiation, SH-S Y5Y cells were treated with the PSA-specific endo-N-acetylneuraminidas e E. Although loss of PSA was accompanied with a marked reduction of c ell growth, it did not interfere with retinoic acid-induced differenti ation. Together, our results suggest that PSA surface expression is re gulated on the level of polysialyltransferase transcription. Moreover, the similarity to the primary neuroblastoma tissue makes SH-SY5Y cell s a suitable model system to examine further the role of polysialylati on in tumor cell growth and the orchestration of PSA synthesis in neur oblastoma.