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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Angiogenesis and expression of PDGF-C, VEGF, CD105 and HIF-1 alpha in human glioblastoma

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Author(s):
Clara, Carlos Afonso [1] ; Marie, Suely K. N. [2] ; Walther de Almeida, Jose Reynaldo [1] ; Wakamatsu, Alda [3] ; Oba-Shinjo, Sueli Mieko [2] ; Uno, Miyuki [2] ; Neville, Munro [4] ; Rosemberg, Sergio [3]
Total Authors: 8
Affiliation:
[1] Univ Sao Paulo, Barretos Canc Hosp, Pio Fdn 12, BR-01246903 Sao Paulo - Brazil
[2] Univ Sao Paulo, Sch Med, Dept Neurol, BR-01246903 Sao Paulo - Brazil
[3] Univ Sao Paulo, Sch Med, Dept Pathol, BR-01246903 Sao Paulo - Brazil
[4] Karolinska Univ, Stockholm - Sweden
Total Affiliations: 4
Document type: Journal article
Source: NEUROPATHOLOGY; v. 34, n. 4, p. 343-352, AUG 2014.
Web of Science Citations: 35
Abstract

Glioblastoma (GBM), the most frequent and aggressive brain tumor, is characterized by marked angiogenesis directly related to invasiveness and poor prognosis. Hypoxia is considered to be an important stimulus for angiogenesis by inducing hypoxia-inducible factor 1-alpha (HIF-1 alpha) overexpression that activates platelet-derived growth factor (PDGF) and VEGF. The aim of this study is to analyze the expression of PDGF-C, VEGFin endothelial and tumor cells of GBM and their relation to HIF-1 alpha expression. Two hundred and eight GBM cases were studied by tissue microarray immunohistochemical preparation. Expression of HIF-1 alpha, VEGF and PDGF-C was observed in 184 (88.5%), 131 (63%) and 160 (76.9%) tumor cases, respectively. The numbers of vessels were quantified by CD34, PDGF-C, VEGF and CD105 staining, and were in median 20, 16, 5 and 6, respectively. The GBMs that showed positive or negative expression for HIF-1 alpha showed a median vascular density of 30 and 14, respectively, for CD34 (P < 0.015). Positive expression for HIF-1 alpha was correlated with VEGF and PDGF-C expression in tumors (P < 0.001). There was a significant correlation between VEGF and PDGF-C expression in the cytoplasm of GBM tumor cells (P < 0.0001). We showed that VEGF expression in tumor cells was correlated with its expression in blood vessels (P < 0.0001). Endothelial cells with PDGF-C and VEGF positive expression were also positive for CD105 and their nuclei for Ki-67, confirming the neoangiogenic and proliferative influence of VEGF and PDGF-C. VEGF nuclear staining in tumor cells (P = 0.002) as well as nuclear staining for HIF-1 alpha and VEGF (P = 0.005) correlated with survival. In summary, our present findings of the concomitant upregulation of PDGF-C with VEGF in GBM tumor cells and vessels further reinforce the benefit of using combined anti-angiogenic approaches to potentially improve the therapeutic response for GBM. (AU)

FAPESP's process: 04/12133-6 - Search for molecular markers related to the diagnosis and prognosis of tumors of the central nervous system
Grantee:Suely Kazue Nagahashi Marie
Support Opportunities: Research Projects - Thematic Grants