Increased expression of cysteine cathepsins in ovarian tissue from chickens with ovarian cancer

Abstract

BackgroundCysteine cathepsins (CTSs) are involved in the degradation and remodeling of the extracellular matrix and are associated with cell transformation, differentiation, motility, and adhesion. These functions are also related to cancer cell invasion and metastasis. Chickens spontaneously develop epithelial ovarian cancer and are therefore a good animal model for human ovarian cancer. However, no studies have investigated the expression of CTSs in chickens with ovarian cancer.MethodsCancerous (n = 5) and normal (n = 3) ovaries were collected from 2-to 3-year-old hens, and ovarian tissue samples were collected for study. Ovarian cancers were evaluated with hematoxylin and eosin staining. Reverse transcriptase and quantitative PCR analyses, in situ hybridization analysis were performed to examine the mRNA expression pattern of three CTSs in detail, and protein expression of CTSB was evaluated.ResultsThe CTSB, CTSC, and CTSS genes were highly expressed in cancerous chicken ovaries. Messenger RNAs for the three CTSs were localized to a nodule area, a major characteristic of cancerous ovaries, but the three CTSs showed no specific localization in normal ovaries. Immunoreactive CTSB protein was present in the nodule area of cancerous ovaries.ConclusionOur results suggest that CTSB, CTSC, and CTSS have important functions in the development of epithelial ovarian cancer.

Chicken Pleiotrophin: Regulation of Tissue Specific Expression by Estrogen in the Oviduct and Distinct Expression Pattern in the Ovarian Carcinomas

“…To investigate and elucidate the etiological and pathological aspects of EOC, several rodent models have been developed through biotechnological manipulation, but they have many limitations and obstacle associated with clinical relevance because of the non-spontaneous nature and physiologically distinct differences in their EOC [17], [32], [33]. Meanwhile, the chicken spontaneously develops EOC at a high rate as occurs in women and shows very similar morphological characteristics to that of EOC in women [17], [18], [19], [20], [21]. Therefore, the chicken EOC could be used to develop anti-cancer drugs and biomarkers for early diagnosis and therapies to prevent adverse outcomes of EOC in women.…”

Avian Prostatic Acid Phosphatase: Estrogen Regulation in the Oviduct and Epithelial Cell-Derived Ovarian Carcinomas1

“…In addition, chicken EOC may arise from the oviduct, and a number of common genes are up-regulated in EOC and in the oviduct in response to estrogen stimulation in the laying hen model [33]. Indeed, we reported expression of several estrogen-stimulated genes in cancerous ovaries of laying hens that include cathepsin B (CTSB) [34], serpin peptidase inhibitor, clade B, member 11 (SERPINB11) [12], SERPINB3 [35], S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) [36], secreted phosphoprotein 1 (SPP1) [12], alpha 2 macroglobulin (A2M) [37], pleiotrophin (PTN) [38], beta-defensin 11 (AvBD-11) [39], beta-catenin (CTNNB1) [40], and several cell cycle genes [41] that are also mainly expressed in the chicken oviduct. Likewise, our current results indicate that expression of ACPP mRNA and protein increase significantly in GE of cancerous, but not normal, ovaries of laying hens.…”

Prostaglandin D2 synthase related to estrogen in the female reproductive tract

“…Interestingly, the merits of the laying hen model are being recognized because mechanisms for progression of EOC and histological/pathological features are similar to EOC in women [12,31,32]. Indeed, we have reported several estrogen-stimulated genes that are expressed in GE of ovarian adenocarcinomas, but not normal ovaries from laying hens and these include cathepsin B (CTSB) [33], serpin peptidase inhibitor, clade B, member 11 (SERPINB11) [13], betadefensin 11 (AvBD-11) [34], and several cell cycle genes [35]. Although Fujimori and colleagues detected PTGDS expression in the ovaries of 24-week-old chickens [23], ovarian carcinoma generally occurs in laying hens that are 4-to 5-years of age.…”