Etiology and Pathogenesis > Kinesins  

Meeting Abstract

Expression of neural specific kinesins in neuronal and glial tumours

Caspani E.¹, Marthyn P.¹, Ceruti S.², Pollo B.³, Abbracchio M. P.² and Navone F.¹

¹CNR Cellular and Molecular Pharmacology Center, Dept. of Medical Pharmacology, Univ. of Milano. ²Dept. of Pharmacological Sciences, Univ. of Milano. ³Istituto Nazionale Neurologico C. Besta, Milano; Italy.

Kinesins are a superfamily of molecular motors that use the energy of ATP hydrolysis to move different types of cargoes (membranes, protein complexes or filaments) along microtubules (MTs). 
The founding member of the kinesin I family is conventional kinesin, composed of two identical kinesin heavy chains containing the motor domain and two identical light chains. 
Kinesin II is a more recently described motor consisting of two distinct subunits complexed with a third nonmotor kinesin associated protein. nKHC (neuronal kinesin) and KIF3C are kinesin motors of the kinesin I and the kinesin II family, respectively. 
We have recently shown that both proteins are selectively expressed in the adult and the developing nervous system and that their expression levels are up-regulated during neuroblastoma differentiation, suggesting a role for these motors during maturation of neuronal cells. 
Comparison of the expression of these neural kinesins in neuronal and glial cells in culture indicates a different pattern of expression for the two motors: while both nKHC and KIF3C are present in SH-SY5Y human neuroblastoma cells, only KIF3C, and not nKHC, can be detected in primary cultures of rat hippocampal astrocytes. 
The specificity of expression of nKHC in neurons became more interesting when samples obtained from tumours of the central nervous system were analysed for the presence of nKHC and KIF3C. 
Our results indicate that the expression of nKHC is strikingly induced in tumours of astrocytic lineage, although it cannot be detected in glial cells of normal human cortex. 
In addition, the quantitative expression of this kinesin appears to be higher in more malignant tumours, although a considerable hetereogeneity of expression is found among samples of tumours of the same grade. 
Similar results were obtained for the presence of KIF3C. 
For comparison, the expression of the ubiquitously present uKHC was analysed in parallel and was found to have little variability among tumours of different malignancy. 
To better understand the possible correlation between the levels of expression of neural specific kinesins and the malignancy of glial tumours, we used astrocytoma and glioblastoma cell lines as an in vitro model for cancer cells characterized by distict differentiation and motility properties. 
We found that all three kinesins are expressed in glioblastoma cells and that nKHC, but not uKHC, can be up-regulated in conditions that are known to modify their adhesive properties, such as serum deprivation.