Expression of the neural cell adhesion molecule and polysialic acid in human neuroblastoma cell lines

The neural cell adhesion molecule NCAM is a cell surface glycoprotein of the immunoglobulin superfamily and is widely expressed in tumours of neuroectodermal origin such as neuroblastoma. NCAM can be decorated by the carbohydrate polymer polysialic acid (polySia), which attenuates NCAM-mediated cell adhesion and increases cellular motility. The key enzymes in the biosynthesis of polySia are the two polysialyltransferases ST8SiaII and ST8SiaIV. In the present study, expression of NCAM, polySia-NCAM, ST8SiaII and ST8SiaIV was investigated in five human neuroblastoma cell lines before and after xenografting into SCID mice by immunohistochemistry, Western blot analysis and real-time PCR. Results were correlated with the metastatic potential. In vitro, three cell lines (LAN-1, LAN-5 and SH-SY5Y) were positive for polySia attached to the transmembrane isoforms NCAM-140 and NCAM-I 80, whereas Kelly and SK-N-SH cells were negative for NCAM and polySia. In the presence of NCAM, the level of polySia correlated with the amount of polysialyltransferase transcripts, which were highest in LAN-1, LAN-5 and SH-SY5Y cells. In the respective primary tumours grown in SCID mice, the expression patterns of NCAM, polySia and polysialyltransferases were similar to those observed in vitro. After subcutaneous engraftment, polySia-NCAM-positive neuroblastoma developed disseminated micrometastases, a metastatic pattern that was not observed for tumours derived from NCAM-negative cell lines. Together, this indicates that the presence of polySia reduces the adhesiveness of tumour cells and promotes dissemination.