Podoplanin increases migration and angiogenesis in malignant glioma.
Expression of podoplanin in glial brain tumors is grade dependent. While serving as a marker for tumor progression and modulating invasion in various neoplasms, little is known about podoplanin function in gliomas. Therefore we stably transfected two human glioma cell lines (U373MG and U87MG) with expression plasmids encoding podoplanin. The efficacy of transfection was confirmed by FACS analysis, PCR and immunocytochemistry. Cells were then sorted for highly podoplanin expressing cells (U373P(high)/U87P(high)). Transfection did not influence the production of pro-angiogenic factors including VEGF, VEGF-C and D. Also, expression of VEGF receptors (VEGFR) remained unchanged except for U87P(high), where a VEGFR3 expression was induced. U373P(high) showed significantly reduced proliferation as compared to mock transfected group. By contrast, podoplanin significantly increased migration and invasion into collagen matrix. Furthermore, conditioned media from P(high) glioma cells strongly induced tube formation on matrigel. In conclusion, podoplanin increased migration of tumor cells and enhanced tube formation activity in endothelial cells independent from VEGF. Thus, podoplanin expression may be an important step in tumor progression.
Department of Neurosurgery, University of Cologne Germany.
Stefan J
SJ
Grau
Department of Gynaecology, University Medical Center Hamburg-Eppendorf, Germany.
Fabian
F
Trillsch
Department of Neurosurgery, Ludwig-Maximilian-University Munich Germany.
Joerg-Christian
JC
Tonn
Department of Gynaecology, University Medical Center Hamburg-Eppendorf, Germany.
Roland H
RH
Goldbrunner
Helmholtz Zentrum Munich Germany.
Elfriede
E
Noessner
Department of Internal Medicine, Ludwig-Maximilian-University Munich Germany.
Peter J
PJ
Nelson
Department of Pediatrics, Technical University Munich Germany.
Irene
I
von Luettichau
D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D019899:Paracrine Communication; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D000098853:Podoplanin
D042501:Angiogenic Proteins; D003094:Collagen; D017077:Culture Media, Conditioned; D008562:Membrane Glycoproteins; C117468:PDPN protein, human; D000098853:Podoplanin
Podoplanin; angiogenesis; glioma