Abstract | OBJECTIVES: METHODS: The mRNA levels of VEGF, NGF and trkA receptors were measured using PCR in 60 ovarian samples. Cellular localization and semi-quantitative estimation of VEGF, NGF, total trkA and p-trkA was performed using IHC in epithelial cells. NGF, total trkA and p-trkA protein were also evaluated in endothelial cells from the same tissues. Human endothelial cell line EA.hy926 was cultured with conditioned media obtained from both EOC explants and from the A2780 cell line, with or without NGF stimulus. RESULTS: Significantly higher levels of NGF, total trkA and p-trkA protein expressions were observed in epithelial and endothelial cells in poorly differentiated EOC versus normal ovary. Interestingly, the p- trkA receptor expression level showed the most significant difference and its presence was only found in borderline tumor and EOC samples indicating the importance of trkA receptor in EOC as a potential tumor marker. A significant increase in proliferation, migration and differentiation of EA.hy926 cells was observed with NGF, and this effect was significantly reverted when NGF was immuno-blocked and when a trkA inhibitor was used, showing that NGF is an important angiogenic factor in EOC by activating its trkA receptor. CONCLUSION:
|
Authors | Verónica Tapia, Fernando Gabler, Marcela Muñoz, Roberto Yazigi, Alfonso Paredes, Alberto Selman, Margarita Vega, Carmen Romero |
Journal | Gynecologic oncology
(Gynecol Oncol)
Vol. 121
Issue 1
Pg. 13-23
(Apr 2011)
ISSN: 1095-6859 [Electronic] United States |
PMID | 21236475
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2010 Elsevier Inc. All rights reserved. |
Chemical References |
- Biomarkers, Tumor
- RNA, Messenger
- VEGFA protein, human
- Vascular Endothelial Growth Factor A
- Nerve Growth Factor
- Receptor, trkA
|
Topics |
- Aged
- Biomarkers, Tumor
(biosynthesis, genetics)
- Carcinoma, Ovarian Epithelial
- Cell Differentiation
(physiology)
- Cell Growth Processes
(physiology)
- Cell Line, Tumor
- Cell Movement
(physiology)
- Female
- Humans
- Immunohistochemistry
- Middle Aged
- Neoplasms, Glandular and Epithelial
(enzymology, genetics, pathology)
- Nerve Growth Factor
(biosynthesis, genetics)
- Ovarian Neoplasms
(enzymology, genetics, pathology)
- RNA, Messenger
(biosynthesis, genetics)
- Receptor, trkA
(biosynthesis, genetics)
- Vascular Endothelial Growth Factor A
(biosynthesis, genetics)
|