Expression of Death Receptor 6 by Ovarian Tumors in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer

Abstract

Tumor-associated neoangiogenesis and suppression of antitumor immunity are hallmarks of tumor development and progression. Death receptor 6 (DR6) has been reported to be associated with suppression of antitumor immunity and tumor progression in several malignancies. However, expression of DR6 by malignant ovarian epithelial tumors at an early stage is unknown. The goals of this study were to determine whether DR6 is expressed by malignant ovarian epithelial tumors at an early stage and to examine whether DR6 expression is associated with ovarian cancer (OVCA) progression in a laying hen model of spontaneous OVCA. Expression of DR6 was examined in normal and malignant ovaries, normal ovarian surface epithelial (OSE) cells, or malignant epithelial cells and in serum of 3-year-old hens. The population of microvessels expressing DR6 was significantly higher in hens with early-stage OVCA than hens with normal ovaries (P < .01) and increased further in late-stage OVCA. The results of this study showed that, in addition to microvessels, tumor cells in the ovary also express DR6 with a significantly higher intensity than normal OSE cells. Similar patterns of DR6 expression were also observed by immunoblot analysis and gene expression studies. Furthermore, DR6 was also detected in the serum of hens. In conclusion, DR6 expression is associated with OVCA development and progression in laying hens. This study may be helpful to examine the feasibility of DR6 as a useful surrogate marker of OVCA, a target for antitumor immunotherapy and molecular imaging and thus provide a foundation for clinical studies.

Association of Interleukin 16 With the Development of Ovarian Tumor and Tumor-Associated Neoangiogenesis in Laying Hen Model of Spontaneous Ovarian Cancer

“…11 Each normal or tumor-bearing ovary was divided into 4 portions for protein extraction, total RNA collection, and paraffin and frozen embedding for routine histology and immunohistochemical studies as reported previously. 3 Normal ovarian surface epithelial cells or epithelial cells of the tumor in OVCA hens were collected similarly as reported earlier.…”

“…11 The histopathology and expression of several markers of OVCA in hens are similar to humans. 11,12 As in humans, IL-16 in chicken is synthesized as a precursor protein (proYIL- 16), with 49% to 52% identity to mammalian homologs. 13 Our goal was to determine whether the serum levels of IL-16 is associated with early-stage ovarian TAN in hens.…”

Orientation of Preclinical Research in Ovarian Cancer

“…Since long it has been known that domestic chicken develop epithelial ovarian cancer spontaneously because of daily ovulation. 59,60 This leads to a spontaneous incidence of ovarian cancer between 5% and 35%, which is higher compared with the incidence in women (1.3%). The metastatic pattern of EOC in the hen is very similar to that in humans; the relative incidence of the different histopathologic subtypes, however, is different.…”

“…In addition, most high-grade ovarian carcinomas are of mucinous histology, and HGSOC is rarely seen. 59 …”

ATL: A Preclinical Model of Spontaneous Ovarian Cancer

“…25,27,28 Similar to OVCA in humans, epithelial ovarian tumors in hens are of 4 histologic subtypes (serous, endometrioid, mucinous, and occasionally clear cell carcinoma). 29 The incidence of serous and endometrioid OVCA are higher than those of mucinous and clear cell OVCA. Ovarian tumors in hens also express several markers similarly expressed by human OVCA.…”