GENETIC ANALYSIS AND FUNCTIONAL CHARACTERIZATIONS OF SEMAPHORIN 5A AND PLEXIN-B3 IN HUMAN GLIOMAS

Abstract

SEMAPHORINS AND THEIR RECEPTORS PLEXINS ARE LARGE FAMILY OF MOLECULES KNOWN TO CONTROL AXON GUIDANCE FUNCTIONS. ACCUMULATING EVIDENCE SUGGESTS THAT THEY ALSO PLAY IMPORTANT ROLE IN A PLETHORA OF BIOLOGICAL PROCESSES RANGING FROM CELL MIGRATION, ANGIOGENESIS, IMMUNE RESPONSES TO CANCER PROGRESSION. WE HAVE RECENTLY DEMONSTRATED THE EFFECTS OF SEMAPHORIN 5A (SEMA5A) IN INHIBITING MIGRATION, INVASION, AND PROLIFERATION IN HUMAN ASTROCYTOMAS THROUGH ITS RECEPTOR PLEXIN-B3. ANALYSIS OF HUMAN ASTROCYTOMA SPECIMENS FROM LOW TO HIGH GRADES REVEALED A MARKED DECLINE IN SEMA5A PROTEIN LEVELS. RECONSTITUTION OF SEMA5A EXPRESSION IN ADVANCED GRADE OF GLIOBLASTOMAS SUCCESSFULLY COUNTERACTS INVASION AND PROLIFERATION OF CANCER CELLS. WE THEREFORE HYPOTHESIZED THAT SEMA5A AND PLEXIN-B3 SUBSERVE TUMOR SUPPRESSOR FUNCTIONS, WHICH ARE COMPROMISED IN GLIOBLASTOMAS DUE TO A DOWNREGULATION OF SEMA5A, HENCE CONTRIBUTING TO HIGH INFILTRATION AND MALIGNANCY. IN THIS STUDY, WE INVESTIGATED THE MECHANISMS UNDER