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Association of Interleukin 16 With the Development of Ovarian Tumor and Tumor-Associated Neoangiogenesis in Laying Hen Model of Spontaneous Ovarian Cancer
  1. Aparna Yellapa, MS*,
  2. Janice M. Bahr, PhD,
  3. Pincas Bitterman, MD,
  4. Jacques S. Abramowicz, MD§,
  5. Seby L. Edassery, MS*,
  6. Krishna Penumatsa, PhD*,
  7. Sanjib Basu, PhD,
  8. Jacob Rotmensch, MD§ and
  9. Animesh Barua, PhD*,,§
  1. *Department of Pharmacology, Rush University Medical Center, Chicago;
  2. Department of Animal Sciences, University of Illinois at Urbana-Champaign; and Departments of
  3. Pathology,
  4. §Obstetrics and Gynecology, and
  5. Preventive Medicine (Biostatistics), Rush University Medical Center, Chicago, IL.
  1. Address correspondence and reprint requests to Animesh Barua, PhD, Department of Pharmacology, Laboratory for Translational Research on Ovarian Cancer, Rush University Medical Center, Room # 410, Cohn Bldg, 1735 W Harrison St, Chicago IL 60612. E-mail:


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.

  • Interleukin 16
  • Ovarian tumor
  • Tumor-associated neoangiogenesis
  • Ovarian cancer

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  • This study was supported by the Idea Development Award from the US Department of Defense (OC#093303) and the Elmer Sylvia and Sramek Foundation (USA).

  • The authors declare that there are no conflicts of interest.