Diffusely infiltrating
gliomas are the most common type of primary
intracranial neoplasm in humans. One of the major obstacles to the effective treatment of these
tumors is their highly infiltrative growth. However, mechanisms controlling their migration and proliferation are poorly understood.
Glioma cells resemble neural progenitors, and we hypothesize that
gliomas recapitulate the capacity of migration and proliferation of progenitors that takes place during brain development. Based on recent evidence implicating
cytoplasmic dynein and its regulatory
proteins in neural progenitor migration and division, we conducted immunohistochemical evaluation of surgically resected human
glioma samples for the presence and distribution of these
proteins. We examined expression of LIS1, the gene responsible for type I
lissencephaly,
cytoplasmic dynein and the
dynein- and LIS1-interacting factors
dynactin, NudE/NudEL and NudC, which play significant roles in neural progenitor cell behavior. We found that each of these
proteins is expressed in all histological types and grades of human
neuroectodermal tumors examined. Immunohistochemical analysis revealed that the levels of expression varied from cell to cell within each
tumor, ranging from very high to undetectable. This stands in contrast to the low levels of diffuse staining seen in non-neoplastic brain tissue. Of particular interest, we noted
tumor cells infiltrating the white matter and
tumor cells undergoing cell division amongst the cells with notably high expression levels. These findings are compatible with the idea that LIS1 and its interacting
proteins play a role in
glioma migration and proliferation analogous to their role during brain development.