Expression of Gonadotropin-Releasing Hormone II (GnRH-II) Receptor in Human Endometrial and Ovarian Cancer Cells and Effects of GnRH-II on Tumor Cell Proliferation

Gründker, Carsten; Günthert, Andreas R.; Millar, Robert P.; Emons, Günter

doi:10.1210/jcem.87.3.8437

Cited by 129 publications

(106 citation statements)

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“…The known receptors can be broadly divided into two forms, GnRH-R I and GnRH-R II. 8,16 The number of patients in our study precludes speculation about association between clinical behavior and heterogeneous GnRH-R I and II expression but immunohistochemical detection of the receptors may identify tumor cells with an autocrine regulatory potential based on GnRH. 9 Interestingly, the five recurrent tumors in our series had high levels of GnRH-R I and II expression.…”

Section: Discussionmentioning

confidence: 95%

“…For immunohistochemical analysis, representative 2-mm-thick sections of the endometrial stromal sarcomas were incubated with guinea-pig antisera to GnRH-R I (1:1000) and GNRH-R II (1:2000) after proteinase pretreatment. The antisera have been preciously characterized 8,9 and were generously provided by PD Dr Gundker, Department of Obstetrics and Gynecology, Georg-August University of Goettingen, Germany. Negative staining was recorded when 0-10% of tumor cells reacted with the antibodies.…”

Section: Methodsmentioning

confidence: 99%

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Gonadotropin-releasing hormone receptor expression in endometrial stromal sarcomas: an immunohistochemical study

2005

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Gonadotropin-releasing hormone and its receptors have been identified in several human malignancies. We evaluated gonadotropin-releasing hormone receptor expression in 30 primary and recurrent endometrial stromal sarcomas. Archival formalin-fixed and paraffin-embedded material was analyzed immunohistochemically with antisera to gonadotropin-releasing hormone receptor type I and gonadotropin-releasing hormone receptor type II using the peroxidase-antiperoxidase method. Gonadotropin-releasing hormone receptor types I and II were demonstrated in most primary endometrial stromal sarcomas in varying intensity and percentage (range, 10-100%). The staining pattern was either diffuse cytoplasmic or granular/vesicular in perinuclear distribution. Recurrences stained stronger than primary tumors. The demonstration of gonadotropin-releasing hormone receptors I and II expression in endometrial stromal sarcomas may be a rationale for a clinical study of gonadotropin-releasing hormone analogs in the treatment of women with endometrial stromal sarcomas.

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Section: Discussionmentioning

confidence: 95%

Section: Methodsmentioning

confidence: 99%

Gonadotropin-releasing hormone receptor expression in endometrial stromal sarcomas: an immunohistochemical study

2005

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“…The GnRH-I antagonist cetrorelix (SB-75; [Ac-DNal (2) 1 , D-Phe(4Cl) 2 , D-Pal(3) 3 , D-Cit 6 , D-Ala 10 ]GnRH-I) was kindly provided by Zentaris (Frankfurt, Germany) and the GnRH-I agonist [D-Trp 6 ]GnRH (triptorelin; pGlu-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH 2 ) was kindly provided by Ferring Pharmaceuticals (Copenhagen, Denmark). Human GnRH-II ( pGlu-HisTrp-Ser-His-Gly-Trp-Tyr-Pro-Gly-NH 2 ) was purchased from Bachem (Heidelberg, Germany).…”

Section: Gnrh Analoguesmentioning

confidence: 99%

“…Recently, we were able to show that GnRH type II (GnRH-II) has antiproliferative effects on these tumour cells that are significantly greater than those of the superactive GnRH-I agonist, triptorelin (6). and ovarian cancers that a putative GnRH-II receptor could be present (6), this might explain why the GnRH-I antagonist cetrorelix behaves like an agonist in reproductive tissue tumours (2 -5).…”

Section: Introductionmentioning

confidence: 99%

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Antiproliferative effects of the GnRH antagonist cetrorelix and of GnRH-II on human endometrial and ovarian cancer cells are not mediated through the GnRH type I receptor

Gründker

Schlotawa

Viereck

et al. 2004

European Journal of Endocrinology

101

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Background: The majority of human endometrial and ovarian cancer cell lines express receptors for GnRH. Their proliferation is time-and dose-dependently reduced by GnRH-I and its superagonistic analogues. Recently, we have demonstrated that, in human endometrial and ovarian cancer cell lines except for the ovarian cancer cell line EFO-27, the GnRH-I antagonist cetrorelix has antiproliferative effects comparable to those of GnRH-I agonists, indicating that the dichotomy between GnRH-I agonists and antagonists might not apply to the GnRH system in cancer cells. We were also able to show that the proliferation of human endometrial and ovarian cancer cells was doseand time-dependently reduced by GnRH-II to a greater extent than by GnRH-I agonists. Objective: In this study we have assessed whether or not the antiproliferative effects of the GnRH-I antagonist cetrorelix in endometrial and ovarian cancer cells are mediated through the GnRH-I receptor. Methods: We analysed the antiproliferative effects of the GnRH-I agonist triptorelin, the GnRH-I antagonist cetrorelix and GnRH-II in a panel of endometrial and ovarian cancer cell lines expressing GnRH-I receptors, in the SK-OV-3 ovarian cancer cell line that does not express GnRH-I receptors, and in four GnRH-I receptor positive GnRH-I receptor knockout cell lines. Results: We found that, after knockout of the GnRH-I receptor, the antiproliferative effects of the GnRH-I agonist triptorelin were abrogated, whereas those of the GnRH-I antagonist cetrorelix and of GnRH-II persisted. Conclusions: These data suggest that, in endometrial and ovarian cancer cells, the antiproliferative effects of cetrorelix and of GnRH-II are not mediated through the GnRH-I receptor.

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LHRHConjugated Magnetic Nanoparticles for Diagnosis and Treatment of Cancers

Leuschner

2003

Nanotechnologies for the Life Sciences

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The sections in this article are Introduction Cancer Conventional Approaches to Cancer/Metastases Detection Current Chemotherapeutic Approaches and their Disadvantages in Cancer Treatments Multidrug Resistance Drug Delivery to Tumors Nanoparticles as Vehicles for Drug Delivery and Diagnosis Targeting Tumor Cells Passive Targeting Active Targeting Detection of Tumors and Metastases using Nanoparticles Nanoparticles for Magnetic Resonance Imaging Targeted Delivery of Nanoparticles to Increase Cellular Uptake for Higher MRI Resolution LHRH and its Receptors The Ligand Luteinizing Hormone Releasing Hormone – LHRH Analogs of LHRH Receptors for LHRH Function–Signal Transduction Pathways LHRH Receptor‐mediated Uptake LHRH Receptor Type II LHRH ‐bound Magnetic Nanoparticles Synthesis and Characterization Treatment using Hyperthermia Treatment using Lytic Peptides Destruction of Metastases through LHRH ‐ SPION ‐Hecate Detection of Tumors and Metastases Targeted Delivery of SPION Contrast Agents for MRI In Vitro Studies on Receptor‐targeted LHRH ‐ SPION Uptake In Vivo Studies on Receptor‐targeted LHRH ‐ SPION Uptake Future Outlook Acknowledgments

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Expression of Gonadotropin-Releasing Hormone II (GnRH-II) Receptor in Human Endometrial and Ovarian Cancer Cells and Effects of GnRH-II on Tumor Cell Proliferation

Cited by 129 publications

References 0 publications

Gonadotropin-releasing hormone receptor expression in endometrial stromal sarcomas: an immunohistochemical study

Gonadotropin-releasing hormone receptor expression in endometrial stromal sarcomas: an immunohistochemical study

Antiproliferative effects of the GnRH antagonist cetrorelix and of GnRH-II on human endometrial and ovarian cancer cells are not mediated through the GnRH type I receptor

LHRHConjugated Magnetic Nanoparticles for Diagnosis and Treatment of Cancers

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