Expression of hCG and GnRHs and Their Receptors in Endometrial Carcinoma and Hyperplasia

Jankowska, Anna; Andrusiewicz, Mirosław; Fischer, Natalia; Warchoł, Jerzy B.

doi:10.1111/igc.0b013e3181bbe933

Cited by 21 publications

(19 citation statements)

References 37 publications

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“…Recently, it was shown that elevated levels of β-hCG in serum, urine or tumor tissue correlates with poor prognosis, aggressiveness and resistance to therapy in a variety of nontrophoblastic tumors, such as bladder, colon, lung (5) and testicular cancer (6). Moreover, it is also ectopically expressed in numerous gynecological malignancies, such as endometrial carcinoma (7), ovarian cancer (8) and cervical carcinoma (9,10). …”

Section: Introductionmentioning

confidence: 99%

Human chorionic gonadotropin β regulates epithelial-mesenchymal transition and metastasis in human ovarian cancer

et al. 2017

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Human chorionic gonadotropin β (β-hCG) is a well-known and accurate marker for the diagnosis and monitoring of pregnancy, trophoblastic tumors and ovarian germ cell tumors. Recently, β-hCG has been found to be closely related to poor prognosis and metastasis in various other malignant tumors, while its role and mechanism in ovarian cancer is still unclear. In the present study, lentiviral-mediated transfection and small interfering RNA (siRNA) were used to alter β-hCG expression in the ovarian cancer cell lines ES-2 and SKOV3, respectively. Then, migration and invasion activity regulated by β-hCG were evaluated by wound-healing and Transwell assays in vitro and in a peritoneal xenograft nude mouse model in vivo. EDTA and trypsin were utilized to investigate the attachment ability of these cells. Moreover, the expression of epithelial mesenchymal transition (EMT) markers (β-catenin, Slug, vimentin, Snail, claudin, E-cadherin and N-cadherin) was assessed by western blotting and immunofluorescence in ES-2 and SKOV3 cells. Furthermore, β-hCG and EMT markers were evaluated in human ovarian cancer specimens by IHC. The results showed that overexpression of β-hCG clearly promoted migration and invasion in ES-2 and SKOV3 cells (P<0.05) and facilitated metastasis in peritoneal xenografts, while silencing of β-hCG led to the opposite effect. Moreover, β-hCG was closely associated with cell morphology, attachment ability and EMT marker expression in ES-2 and SKOV3 cells and human ovarian cancer specimens. Upregulation of β-hCG promoted cells from an epithelial-like morphology to a mesenchymal-like phenotype, decreased the adhesion ability (P<0.05), and reduced the expression of epithelial markers (E-cadherin) while inducing the expression of mesenchymal markers (vimentin, N-cadherin, β-catenin and Slug). Furthermore, the converse effects were confirmed by knockdown of β-hCG. These findings strongly suggest that β-hCG may regulate metastasis of ovarian cancer through EMT, and it may become a new target for therapeutic intervention.

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Section: Introductionmentioning

confidence: 99%

Human chorionic gonadotropin β regulates epithelial-mesenchymal transition and metastasis in human ovarian cancer

et al. 2017

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“…These two genes were selected because a number of studies have demonstrated that their expression level is up-regulated in gynecological tumors [ 32 - 38 ].…”

Section: Introductionmentioning

confidence: 99%

CGB and GNRH1 expression analysis as a method of tumor cells metastatic spread detection in patients with gynecological malignances

et al. 2011

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BackgroundMetastasis is a common feature of many advanced stage cancers and metastatic spread is thought to be responsible for cancer progression. Most cancer cells are localized in the primary tumor and only a small population of circulating tumor cells (CTC) has metastatic potential. CTC amount reflects the aggressiveness of tumors, therefore their detection can be used to determine the prognosis and treatment of cancer patients.The aim of this study was to evaluate human chorionic gonadotropin beta subunit (CGB) and gonadoliberin type 1 (GNRH1) expression as markers of tumor cells circulating in peripheral blood of gynecological cancer patients, indicating the metastatic spread of tumor.MethodsCGB and GNRH1 expression level in tumor tissue and blood of cancer patients was assessed by real-time RT-PCR. The data was analyzed using the Mann-Whitney U and Spearman tests. In order to distinguish populations with homogeneous genes' expression the maximal likelihood method for one- and multiplied normal distribution was used.ResultReal time RT-PCR results revealed CGB and GNRH1 genes activity in both tumor tissue and blood of gynecological cancers patients. While the expression of both genes characterized all examined tumor tissues, in case of blood analysis, the transcripts of GNRH1 were found in all cancer patients while CGB were present in 93% of patients. CGB and GNRH1 activity was detected also in control group, which consisted of tissue lacking cancerous changes and blood of healthy volunteers. The log-transformation of raw data fitted to multiplied normal distribution model showed that CGB and GNRH1 expression is heterogeneous and more than one population can be distinguished within defined groups.Based on CGB gene activity a critical value indicating the presence of cancer cells in studied blood was distinguished. In case of GNRH1 this value was not established since the results of the gene expression in blood of cancer patients and healthy volunteers were overlapping. However one subpopulation consists of cancer patient with much higher GNRH1 expression than in control group was found.ConclusionsAssessment of CGB and GNRH1 expression level in cancer patients' blood may be useful for indicating metastatic spread of tumor cells.

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“…The associations between the expression of LHCGR, the addition of LH/hCG and cell invasiveness should be substantiated in primary endometrial tissue samples and in cell lines. The results of previous studies have suggested that LHCGR + patients may benefit from a therapeutic strategy involving gonadotropin-releasing hormone (GnRH) analogues, since they were demonstrated to reduce the levels of LH (20,21). Furthermore, it has been reported that hCG regulates the expression of VEGF (22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

Influence of VEGFR and LHCGR on endometrial adenocarcinoma

et al. 2016

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Abstract. Endometrial adenocarcinoma is a common gynecological malignancy that is usually treated by surgical resection followed by radiation. However, the frequency of remote metastasis is high. The present study aimed to investigate whether patients with endometrial adenocarcinoma exhibited a positive response to treatment with a gonadotropin-releasing hormone analogue or inhibitors of neoangiogenesis, which are applied for the treatment of other malignancies. Immunohistochemical analyses were performed using 203 paraffin-embedded tissue samples of endometrial adenocarcinomas from patients who had undergone surgery at the Department of Obstetrics and Gynecology of the Ludwig Maximilians University of Munich, Germany. The tissues were incubated with antibodies against luteinizing hormone/choriogonadotropin receptor (LHCGR) and vascular endothelial growth factor receptor 2 (VEGFR2), and evaluated by bright field microscopy. The staining was categorized according to the Immune-Reactive-Score (IRS). The IRS scores were then statistically associated with various tumor traits, including tumor size, lymph node status, metastasis, grade, expression of steroid hormone receptors and patient survival. There was a significant association between VEGFR2 expression and tumor grading and estrogen receptor-α (ERα). For LHCGR, a correlation was observed with ERα and progesterone receptor (PR). No correlations were identified between VEGFR2 or LHCGR expression and the other examined tumor traits or patient survival. The associations between VEGFR2 and ERα, and between LHCGR and ERα or PR, may be explained by the interaction of these signal transduction molecules in the regulation of cellular growth and differentiation. These mechanisms also have an important role in the formation of remote metastases, which is the main cause for tumor-associated mortality. The results of the present study suggested that patients with endometrial adenocarcinoma may benefit from treatment with inhibitors of ERα, PR, VEGFR2 or LHCGR, since it could lead to a better prognosis. However, further studies are required in order to elucidate the roles of these receptors in endometrial adenocarcinoma.

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Expression of hCG and GnRHs and Their Receptors in Endometrial Carcinoma and Hyperplasia

Cited by 21 publications

References 37 publications

Human chorionic gonadotropin β regulates epithelial-mesenchymal transition and metastasis in human ovarian cancer

Human chorionic gonadotropin β regulates epithelial-mesenchymal transition and metastasis in human ovarian cancer

CGB and GNRH1 expression analysis as a method of tumor cells metastatic spread detection in patients with gynecological malignances

Influence of VEGFR and LHCGR on endometrial adenocarcinoma

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