Involvement of sialidase Neu4L in nervous system tumors

The aberrant expression of sialoglycoconjugates characterizes cancer. Sialidases which cleave sialic acid residues seem to be involved in these phenomena and are severely impaired during carcinogenesis. Sialidase Neu4 is coded as two forms, long (Neu4L) and short, and is rarely expressed in adult tissues. Here, we demonstrated that Neu4L expression is unusually high in two nervous system tumors and is involved in the control of proliferation/self-renewal. Neuroblastoma SK-N-BE cells were transfected with Neu4L cDNA. This induced a marked acceleration of proliferation, assessed by an increase of [3H]thymidine incorporation (+ 45%) and by growth curve (+ 36%). After serum withdrawal, Neu4L over-expressing SK-N-BE cells failed to block, enhancing the expression of cyclin D1 and cyclin D2. The direct substrates of Neu4L in SK-N-BE cells were identified as soluble glycoproteins around 60 kDa. In glioblastoma, we discovered a significantly high expression of Neu4L in stem cells isolated from U87 cell line, opposed to the bulk of the cells which constitutes the tumor, in which Neu4L is scarcely relievable. Also, in this case, Neu4L seems to be related to an undifferentiated/self renewal phenotype.