Altered expression of alpha-dystroglycan subunit in human gliomas.
Dystroglycan (DG) is an integral membrane receptor of extracellular matrix proteins, composed of two subunits alpha and beta derived from a common precursor. In brain DG is expressed in neurons, glia limitans, astrocytic endfeet around vessels and endothelial cells. We investigate whether DG may play a role in brain tumors. Western blot and immunofluorescence analysis showed that, while beta-DG subunit was present, the highly glycosylated alpha-DG subunit was strongly reduced in surgically derived human glioblastoma biopsies, in low passage patient-derived cultures and in glioma cell lines, U87MG and A172MG, but not in all glioma cell lines tested. Immunohistochemistry of tumor frozen sections revealed that the loss of alpha-DG was confined in the tumor area but not around blood vessels. Overexpression of DG decreased the growth rate of the glioma cell lines lacking the highly glycosylated alpha-DG subunit and the colony-forming efficiency. Clonogenic assay in presence of temozolomide showed an additive effect between DG overexpression and drug treatment. Our data suggest that DG may be involved in the progression of primary brain tumors.
Dipartimento di Medicina Sperimentale e di Patologia, Università di Roma "La Sapienza", Rome, Italy.
Antonella
A
Calogero
Ernesto
E
Pavoni
Tiziana
T
Gramaglia
Giulia
G
D'Amati
Giuseppe
G
Ragona
Andrea
A
Brancaccio
Tamara C
TC
Petrucci
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000196:embryology; D001932:Brain Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D049030:Dystroglycans / Q000737:chemistry / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D051381:Rats; D014162:Transfection
D049030:Dystroglycans