Platelet-derived growth factor and its receptors in human glioma tissue: expression of messenger RNA and protein suggests the presence of autocrine and paracrine loops.
The expression of platelet-derived growth factor (PDGF) and its receptors was analyzed in 14 gliomas of various degrees of malignancy and compared with three gliosis cases by in situ hybridization and immunohistochemistry techniques. Expression of both PDGF A- and B-chains was higher in glioblastomas than in astrocytomas. The PDGF A-chain mRNA was predominantly found in cell-rich areas in glioblastomas. The cognate PDGF-alpha receptor (PDGFR-alpha) mRNA was heterogeneously distributed in gliomas of all grades, and PDGFR-alpha expression was higher in gliomas than in gliosis. Within some glioblastomas probed with PDGFR-alpha complementary RNA, cells heavily loaded with grains were intermingled with others containing low or moderate signals. The heavily labeled cells were often found in the vicinity of proliferating capillaries. Immunostaining with an anti-PDGF antibody and an affinity-purified antiserum against the PDGFR-alpha showed strong staining of most tumor cells with both antibodies in glioblastoma. In addition, the PDGFR-alpha antibodies yielded a strong staining of scattered cells, and the anti-PDGF antibody yielded staining of a few cells within the astrocytoma. Furthermore, high levels of the PDGF-beta receptor (PDGFR-beta) and PDGF B-chain mRNA as well as the beta receptor protein were found in hyperplastic capillaries. These results suggest the presence of autocrine and paracrine loops in glioma, activating the PDGFR-alpha in glioma cells and the PDGFR-beta in endothelial cells.
Hermanson
M
M
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Funa
K
K
Hartman
M
M
Claesson-Welsh
L
L
Heldin
C H
CH
Westermark
B
B
Nistér
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D001932:Brain Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D002196:Capillaries / Q000473:pathology; D005260:Female; D005910:Glioma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D046911:Macromolecular Substances; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D010982:Platelet-Derived Growth Factor / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000235:genetics; D017479:Receptors, Platelet-Derived Growth Factor
D046911:Macromolecular Substances; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017479:Receptors, Platelet-Derived Growth Factor