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PAX2 induces vascular-like structures in normal ovarian cells and ovarian cancer.

ABSTRACT: In adult tissue, the paired box 2 (PAX2) protein is expressed in healthy oviductal, but not normal ovarian surface epithelial cells. PAX2 is expressed in a subset of cases of serous ovarian carcinoma; however, the role of PAX2 in the initiation and progression of ovarian cancer remains unknown. The aim of the present study was to determine the biological effects of PAX2 expression in normal and cancerous epithelial cells. By culturing the normal and cancerous ovarian cells that express PAX2 in 3D culture and staining the cells with vasculogenic mimicry markers such as CD31 and PAS, it was shown that PAX2 overexpression in both normal and cancerous ovarian epithelial cells induced formation of vascular-like structures both in vitro and in vivo. These results indicated a potential role of PAX2 in ovarian cancer progression by increasing the presence of vascular-like structures to promote the supply of nutrients to tumor cells and facilitate cancer cell proliferation and invasion.

SUBMITTER: Alwosaibai K

PROVIDER: S-EPMC9117948 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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PAX2 induces vascular-like structures in normal ovarian cells and ovarian cancer.

Alwosaibai Kholoud K Al-Hujaily Ensaf M EM Alamri Salmah S Ghandorah Salim S Garson Kenneth K Vanderhyden Barbara C BC

Experimental and therapeutic medicine 20220427 6

In adult tissue, the paired box 2 (PAX2) protein is expressed in healthy oviductal, but not normal ovarian surface epithelial cells. PAX2 is expressed in a subset of cases of serous ovarian carcinoma; however, the role of PAX2 in the initiation and progression of ovarian cancer remains unknown. The aim of the present study was to determine the biological effects of PAX2 expression in normal and cancerous epithelial cells. By culturing the normal and cancerous ovarian cells that express PAX2 in 3 ...[more]

PMID: 35601066

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Project description:Ovarian tumors of low malignant potential and low-grade ovarian serous carcinomas are thought to represent different stages on a tumorigenic continuum and to develop along pathways distinct from high-grade ovarian serous carcinoma. We performed gene expression profiling on three normal human ovarian surface epithelia samples, and 10 low-grade and 10 high-grade ovarian serous carcinomas. Analysis of gene expression profiles of these samples has identified 80 genes upregulated and 232 genes downregulated in low-grade ovarian serous carcinomas. PAX2 was found to be one of the most upregulated genes in low-grade ovarian serous carcinoma. The upregulation of PAX2 was validated by real-time quantitative RT-PCR, western blot and immunohistochemical analyses. Real-time RT-PCR showed a statistically significant difference in PAX2 mRNA expression (expressed as fold change in comparison to normal human ovarian surface epithelia) among ovarian tumors of low malignant potential (1837.38, N=8), low-grade (183.12, N=17), and high-grade (3.72, N=23) carcinoma samples (P=0.015). Western blot analysis revealed strong PAX2 expression in ovarian tumors of low malignant potential (67%, N=3) and low-grade carcinoma samples (50%, N=10) but no PAX2 protein expression in high-grade carcinomas (0%, N=10). Using immunohistochemistry, tumors of low malignant potential (59%, N=17) and low-grade carcinoma (63%, N=16) samples expressed significantly stronger nuclear staining than high-grade ovarian carcinoma samples (9.1%, N=263). Furthermore, consistent with earlier immunohistochemical findings, PAX2 expression was expressed in the epithelial cells of fallopian tubes but not in normal ovarian surface epithelial cells. Our findings further support the two-tiered hypothesis that tumors of low malignant potential and low-grade ovarian serous carcinoma are on a continuum and are distinct from high-grade ovarian carcinomas. In addition, the absence of PAX2 expression in normal ovarian epithelia but expression in fallopian tube fimbria and ciliated epithelial inclusions would suggest the potential development of tumors of low malignant potential and of low-grade ovarian serous carcinomas from secondary Müllerian structures.

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PAX2 induces vascular-like structures in normal ovarian cells and ovarian cancer.

Publications

PAX2 induces vascular-like structures in normal ovarian cells and ovarian cancer.

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