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Role of Hydroxysteroid Dehydrogenase-Like 2 (HSDL2) in Human Ovarian Cancer.

ABSTRACT: BACKGROUND Ovarian cancer is a common type of malignant neoplasm. Its prognosis is poor because the disease is not well understood. Abnormal lipometabolism in peroxisomes is involved in tumor progression and hydroxysteroid dehydrogenase-like 2 (HSDL2), localized in peroxisomes, might be a regulatory factor in lipometabolism. However, the role of HSDL2 in ovarian cancer progression remains unknown. MATERIAL AND METHODS HSDL2 expression was detected by qPCR and immunohistochemistry in ovarian tumor samples and qPCR in human ovarian cancer cell lines. Cell proliferation was measured by Celigo and MTT assay. Cell cycle distribution and apoptosis were determined using flow cytometry. Giemsa staining was used for analyzing colony formation. Cell motility was performed using Transwell migration and invasion assays. Tumorigenesis in nude mice was also detected. RESULTS HSDL2 expression was upregulated in human ovarian cancer samples and in 3 human ovarian cancer cell lines: SKOV3, HO8910, and OVCAR-3. Higher expression of HSDL2 in ovarian tumor samples was associated with more progressed tumors (P=0.03) and lymphatic metastases (P=0.03). HSDL2 down-regulation by lentiviral-mediated HSDL2 knockdown suppressed cell proliferation, colony formation, and cell motility, while it promoted cell apoptosis and resulted in cell cycle arrest at the G0/G1 phase in human ovarian cancer cell lines OVCAR-3 and SKOV3. HSDL2 knockdown also inhibited tumorigenesis in mouse models. CONCLUSIONS This study shows that HSDL2 upregulation is associated with ovarian cancer progression. HSDL2 knockdown inhibited cell proliferation, colony formation, motility, and tumorigenesis. It induced apoptosis and cell cycle arrest and might therefore serve as a potential target for ovarian cancer therapy.

SUBMITTER: Sun Q

PROVIDER: S-EPMC6029517 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Role of Hydroxysteroid Dehydrogenase-Like 2 (HSDL2) in Human Ovarian Cancer.

Sun Qing Q Zhang Yilin Y Su Juanjuan J Li Tiechen T Jiang Yuxin Y

Medical science monitor : international medical journal of experimental and clinical research 20180612

BACKGROUND Ovarian cancer is a common type of malignant neoplasm. Its prognosis is poor because the disease is not well understood. Abnormal lipometabolism in peroxisomes is involved in tumor progression and hydroxysteroid dehydrogenase-like 2 (HSDL2), localized in peroxisomes, might be a regulatory factor in lipometabolism. However, the role of HSDL2 in ovarian cancer progression remains unknown. MATERIAL AND METHODS HSDL2 expression was detected by qPCR and immunohistochemistry in ovarian tumo ...[more]

PMID: 29894468

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Project description:BackgroundRecent studies have shown that production of cortisol not only takes place in several non-adrenal peripheral tissues such as epithelial cells but, also, the local inter-conversion between cortisone and cortisol is regulated by the 11?-hydroxysteroid dehydrogenases (11?-HSDs). However, little is known about the activity of this non-adrenal glucocorticoid system in cancers.MethodsThe presence of a functioning glucocorticoid system was assessed in human skin squamous cell carcinoma (SCC) and melanoma and further, in 16 epithelial cell lines from 8 different tissue types using ELISA, western blotting and immunofluorescence. 11?-HSD2 was inhibited both pharmacologically and by siRNA technology. Naïve CD8+ T cells were used to test the paracrine effects of cancer-derived cortisol on the immune system in vitro. Functional assays included cell-cell adhesion and cohesion in two- and three-dimensional models. Immunohistochemical data of 11?-HSD expression were generated using tissue microarrays of 40 cases of human SCCs as well as a database featuring 315 cancer cases from 15 different tissues.ResultsWe show that cortisol production is a common feature of malignant cells and has paracrine functions. Cortisol production correlated with the magnitude of glucocorticoid receptor (GR)-dependent inhibition of tumour-specific CD8+ T cells in vitro. 11?-HSDs were detectable in human skin SCCs and melanoma. Analyses of publicly available protein expression data of 11?-HSDs demonstrated that 11?-HSD1 and -HSD2 were dysregulated in the majority (73%) of malignancies. Pharmacological manipulation of 11?-HSD2 activity by 18?-glycyrrhetinic acid (GA) and silencing by specific siRNAs modulated the bioavailability of cortisol. Cortisol also acted in an autocrine manner and promoted cell invasion in vitro and cell-cell adhesion and cohesion in two- and three-dimensional models. Immunohistochemical analyses using tissue microarrays showed that expression of 11?-HSD2 was significantly reduced in human SCCs of the skin.ConclusionsThe results demonstrate evidence of a cancer-associated glucocorticoid system and show for the first time, the functional significance of cancer-derived cortisol in tumour progression.

Dataset Information

Role of Hydroxysteroid Dehydrogenase-Like 2 (HSDL2) in Human Ovarian Cancer.

Publications

Role of Hydroxysteroid Dehydrogenase-Like 2 (HSDL2) in Human Ovarian Cancer.

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