title: Association of interleukin 16 with the development of ovarian tumor and tumor-associated neoangiogenesis in laying hen model of spontaneous ovarian cancer.
abstract: OBJECTIVE
  Tumor-associated neoangiogenesis (TAN) is an early event in ovarian tumor development. Interleukin 16 (IL-16) is a proangiogenic cytokine that stimulates production of neoangiogenic factors. The goal of this study was to determine the association of IL-16 with tumor development and ovarian TAN in laying hens, an animal model of spontaneous ovarian cancer (OVCA).
  
  
  METHODS
  Sera and ovarian tissues from 3-year-old laying hens were collected and processed for histopathologic, immunoassay, immunohistochemistry, immunoblotting, and molecular biological studies to determine the tissue expression and serum levels of IL-16. Samples were divided into 3 groups based on the diagnosis of the histopathologic ovarian tissue examination, namely, normal (healthy control, n = 81), early (n = 23 including 11 with microscopic OVCA), and late stages (n = 16) of OVCA.
  
  
  RESULTS
  Serum levels of IL-16 were significantly higher in hens with microscopic, early, and late stages of OVCA than normal hens (P < 0.0001). The frequencies of IL-16 cells in tumor-bearing ovaries were significantly higher than normal hens (P < 0.05). The expression of IL-16 protein and mRNA were stronger in tumor-bearing ovaries than normal ovaries. In addition to ovarian stroma, IL-16 was also expressed by the epithelial cells of the tumor in OVCA hens. Differences in serum levels and ovarian IL-16 expression were not significant among different histological subtypes of OVCA including serous, endometrioid, and mucinous. Similar to the serum levels and ovarian expression of IL-16, the densities of neoangiogenic microvessels were significantly higher in hens with tumor-bearing ovaries than normal hens.
  
  
  CONCLUSIONS
  The results of the study suggest that changes in serum levels of IL-16 are associated with tumor development and TAN. Thus, serum IL-16 levels may be an indicator of ovarian TAN at the early stage of OVCA.
authors.affiliation: Department of Pharmacology, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Aparna
authors.initials: A
authors.lastname: Yellapa
authors.forename: Janice M
authors.initials: JM
authors.lastname: Bahr
authors.forename: Pincas
authors.initials: P
authors.lastname: Bitterman
authors.forename: Jacques S
authors.initials: JS
authors.lastname: Abramowicz
authors.forename: Seby L
authors.initials: SL
authors.lastname: Edassery
authors.forename: Krishna
authors.initials: K
authors.lastname: Penumatsa
authors.forename: Sanjib
authors.initials: S
authors.lastname: Basu
authors.forename: Jacob
authors.initials: J
authors.lastname: Rotmensch
authors.forename: Animesh
authors.initials: A
authors.lastname: Barua
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D002645:Chickens; D004195:Disease Models, Animal; D005260:Female; D019410:Interleukin-16 / Q000097:blood*; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000097:blood / Q000175:diagnosis / Q000473:pathology; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D019410:Interleukin-16