title: Tyrosine kinase A receptor (trkA): a potential marker in epithelial ovarian cancer.
abstract: OBJECTIVE
  To evaluate the role of trkA receptor as a potential tumor marker in serous epithelial ovarian cancer and its relationship with the angiogenic factors expression as vascular endothelial growth factor (VEGF) and nerve growth factor (NGF). Additionally, to examine whether NGF and VEGF secreted by epithelial ovarian cancer (EOC) explants and from epithelial ovarian cancer cell line (A2780) are involved in the process of angiogenesis, such as cellular proliferation, migration and differentiation of the human endothelial cell line (EA.hy926).
  
  
  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.
  
  
  CONCLUSIONS
  These results indicate that p-trkA may be considered as a new potential tumor marker in EOC, and that NGF may also act as a direct angiogenic factor in EOC.
authors.affiliation: Laboratory of Endocrinology and Reproductive Biology, Clinical Hospital, University of Chile, Chile.
authors.forename: Verónica
authors.initials: V
authors.lastname: Tapia
authors.forename: Fernando
authors.initials: F
authors.lastname: Gabler
authors.forename: Marcela
authors.initials: M
authors.lastname: Muñoz
authors.forename: Roberto
authors.initials: R
authors.lastname: Yazigi
authors.forename: Alfonso
authors.initials: A
authors.lastname: Paredes
authors.forename: Alberto
authors.initials: A
authors.lastname: Selman
authors.forename: Margarita
authors.initials: M
authors.lastname: Vega
authors.forename: Carmen
authors.initials: C
authors.lastname: Romero
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D000077216:Carcinoma, Ovarian Epithelial; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D020932:Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020917:Receptor, trkA / Q000096:biosynthesis* / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020932:Nerve Growth Factor; D020917:Receptor, trkA