Mentlein_2011_Biol.Chem_392_199

Seprase or fibroblast activation protein-alpha (FAP-alpha) is a cell-surface serine protease that was previously described nearly exclusively on reactive and tumor stromal fibroblasts and thought to be involved in tissue remodeling. We investigated the expression and significance of FAP-alpha in astrocytomas/glioblastomas. As shown by quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry, FAP-alpha was elevated in whole glioblastoma tissues and in particular in most glioma cells in situ and in vitro. In glioma stem-like cells (gliospheres), FAP-alpha was detected at low levels; however, FAP-alpha was considerably induced upon differentiation with 10% fetal calf serum. To explore its functional role, FAP-alpha was silenced by siRNA transfection. In Boyden chamber assays, FAP-alpha silenced cells migrated similar as control cells through non-coated or Matrigel (basal lamina)-coated porous membranes, but significantly slower through membranes coated with gelatin or brevican, a major component of brain extracellular matrix. Furthermore, FAP-alpha-silenced glioma cells migrated through murine brain slices much slower under the conditions tested than differentially fluorescent-labeled control cells. Thus, FAP-alpha is highly expressed on the surface of glioma cells and contributes to diffuse glioma invasion through extracellular matrix components.