Molecular markers for astrocytic tumors, based on signaling

The prognosis for patients with malignant astroglial tumors is poor. The capacity of astrocytomas both to invade adjacent brain sites and to migrate into distant ones precludes curative surgical resection; and little progress has been made in designing adjuvant therapies that significantly affect long-term survival. In order to formulate more novel therapeutic strategies, it is essential to have a better understanding of how the invasive growth of these tumors is controlled.
The primary interest of the Husseini laboratory is the regulation of LRP (low density lipoprotein receptor-related protein) expression and function in astrocytic tumor cells.  LRP is an endocytic receptor involved in the trafficking of a variety of protein/protein complexes that have pathophysiologic relevance in the central nervous system, including urokinase (uPA) and its receptor (uPAR), lipoprotein metabolites, and activated a2 macroglobulin. Changes in LRP expression may regulate the levels of modulators (uPA, uPAR and PAI-1) of migration/invasion around the microenvironment of astrocytic tumors (Grant: NS35122).

The second project in the laboratory focuses on understanding differences in PKC-h activation and expression between malignant vs. non-neoplastic astrocytes and on the role of PKC-h in the control of cell proliferation and apoptosis. The regulation of cell proliferation and apoptosis in malignant astrocytic tumors is undoubtedly complex; however, they are investigating how PKC-h regulation of these processes may be exploited to provide an experimental system in which proliferative or apoptotic phenotype may be selectively induced and studied. They are also extrapolating some of their results in cultured cells to glioblastoma animal models. They hypothesize that pharmacological regulation of PKC-h, in combination with drugs targeting cellular migration, may present a new therapeutic paradigm for these aggressive brain tumors (Grant: CA90851).