Nestin, PDGFRbeta, CXCL12 and VEGF in glioma patients: different profiles of (pro-angiogenic) molecule expression are related with tumor grade and may provide prognostic information.
Angiogenesis is a key event in the natural progression of gliomas. Nestin, a marker for multipotential neuroepithelial stem cells, is detected in neuroepithelial tumors and in proliferating endothelial cells (ECs) and is involved in the early stages of lineage commitment, proliferation and differentiation. Nestin expression is correlated with proangiogenic chemokines (CXCL12 and its receptor CXCR4) and growth factors (VEGF, PDGF-B and its receptor PDGFRbeta). VEGF expression upregulates CXCR4 on endothelial cells, binding the chemokine SDF1/CXCL12 (Stromal Derived Factor) that has a role on angiogenesis and chemotaxis of endothelial cells; PDGF (platelet-derived growth factor) and PDGFRbeta are also crucial by increasing the expression of VEGF. We performed a retrospective study on the presence and role of nestin-expressing cells in 102 patients with glioma, relating the findings to VEGF, CXCL12, PDGFRbeta expression and to clinical outcome (time to tumor progression-TTP and survival time-ST). Our results suggest that in gliomas the detection of proliferating ECs expressing nestin correlates to histological malignancy grade and clinical outcome. Also, the expression of CXCL12 in low-grade gliomas was the only factor associated with a significantly shorter TTP, suggesting a role of this chemokine in angiogenic shift and/or disease progression.
Maderna
Emanuela
E
Department of Neuropathology, Fonoazione IRCCS, Istituto Nazionale Neurologico "Carlo Besta", Milano, Italy.
Salmaggi
Andrea
A
Calatozzolo
Chiara
C
Limido
Lucia
L
Pollo
Bianca
B
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D054377:Chemokine CXCL12 / Q000032:analysis*; D005260:Female; D005910:Glioma / Q000098:blood supply* / Q000737:chemistry / Q000401:mortality / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000032:analysis*; D064231:Nestin; D011379:Prognosis; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000032:analysis*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; D042461:Vascular Endothelial Growth Factor A; D020797:Receptor, Platelet-Derived Growth Factor beta