Characterization of luteinizing hormone-releasing hormone receptor type I (LH-RH-I) as a potential molecular target in OCM-1 and OCM-3 human uveal melanoma cell lines

Sipos, Éva; Dobos, Nikoletta; Rózsa, Dávid; Fodor, Klara; Oláh, Gábor; Szabó, Zsuzsanna; Székvölgyi, Lóránt; Schally, Andrew V.; Halmos, Gábor

doi:10.2147/ott.s148174

Cited by 5 publications

(3 citation statements)

References 58 publications

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“…In the present study our aim was to demonstrate the antitumor effects of AEZS-108 in a human uveal melanoma cell line. As we reported it previously OCM3 UM cell line express the receptor of LHRH localized on the cell membrane and in the cytoplasm, rendering them susceptible to AEZS-108 uptake [33,34]. The detection of LHRH receptor in OCM3 cells has led to use AEZS-108 for targeted therapy of the tumor.…”

Section: Research Papermentioning

confidence: 79%

The targeted LHRH analog AEZS-108 alters expression of genes related to angiogenesis and development of metastasis in uveal melanoma

et al. 2020

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Uveal melanoma (UM) is the most common malignant tumor of the eye. Recently, we have established that 46% of UM specimens express LHRH receptors. This finding supports the idea of a LHRH receptor-targeted therapy of UM patients. Cytotoxic analog of LHRH, AEZS-108 exhibits effective anti-cancer activity in LHRH-receptor positive cancers. AEZS-108 is a hybrid molecule, composed of a synthetic peptide carrier and the cytotoxic doxorubicin (DOX). In the present study, we investigated AEZS-108 induced cytotoxicity and the altered mRNA expression profile of regulatory factors related to angiogenesis and metastasis in LHRH receptor positive OCM3 cells. Our results show that AEZS-108 upregulates the expression of MASPIN/SERPINB5 tumor suppressor gene, which is downregulated in normal uvea and UM specimens independently from the LHRH receptor-ligand interaction. AEZS-108 also substantially downregulates hypoxia-inducible factor 1 alpha (HIF1A) expression. In order to investigate the mechanism of the induction of MASPIN by AEZS-108, OCM3 cells were treated with free DOX, D-Lys 6 LHRH analog, or AEZS-108. qRT-PCR analysis revealed in OCM3 cells that AEZS-108 is a more potent inducer of MASPIN than free DOX. In conclusion, we show for the first time that AEZS-108 has a major impact in the regulation of angiogenesis thus plays a potential role in tumor suppression. Taken together, our results support the development of novel therapeutic strategies for UM focusing on LHRH receptors.

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Section: Research Papermentioning

confidence: 79%

The targeted LHRH analog AEZS-108 alters expression of genes related to angiogenesis and development of metastasis in uveal melanoma

et al. 2020

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“…Despite the improvement in the diagnosis and therapy of primary UM, the number of metastatic deaths has not been significantly reduced over the past 20 to 30 years [ 44 , 45 ]. Therefore, innovative therapeutic methods are urgently awaited [ 24 , 25 , 46 , 47 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

Somatostatin Receptors as Molecular Targets in Human Uveal Melanoma

Harda

Szabó

et al. 2018

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Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, with an incidence of 4–5 cases per million. The prognosis of UM is very poor. In the present study, our aim was to investigate the expression of mRNA and protein for somatostatin receptor types-1, -2, -3, -4, -5 (SSTR-1–5) in human UM tissue samples and in OCM-1 and OCM-3 human UM cell lines by qRT-PCR, western blot and ligand competition assay. The mRNA for SSTR-2 showed markedly higher expression in UM tissues than SSTR-5. The presence of SSTRs was demonstrated in 70% of UM specimens using ligand competition assay and both human UM models displayed specific high affinity SSTRs. Among the five SSTRs, the mRNA investigated for SSTR-2 and SSTR-5 receptors was strongly expressed in both human UM cell lines, SSTR-5 showing the highest expression. The presence of the SSTR-2 and SSTR-5 receptor proteins was confirmed in both cell lines by western blot. In summary, the expression of somatostatin receptors in human UM specimens and in OCM-1 and OCM-3 human UM cell lines suggests that they could serve as a potential molecular target for therapy of UM using modern powerful cytotoxic SST analogs targeting SSTR-2 and SSTR-5 receptors.

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“…However, in human cancers, their signaling pathways are different [ 16 ]. LHRH receptors have been found on breast, prostatic, ovarian, endometrial, pancreatic cancers, renal cell carcinoma, and uveal melanoma [ 9 , 12 , 15 , 17 , 18 , 19 , 20 ]. LHRH receptors were also found in human benign prostatic hyperplasia [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Expression of Luteinizing Hormone-Releasing Hormone (LHRH) and Type-I LHRH Receptor in Transitional Cell Carcinoma Type of Human Bladder Cancer

et al. 2021

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Bladder cancer (BC) is the tenth most frequently detected cancer in both sexes. Type-I luteinizing hormone-releasing hormone (LHRH) receptor (LHRH-R-I) is expressed not only in the pituitary, but also in several types of cancer disease. There are few data about LHRH-R-I expression in human BC. This study aimed to investigate the expression of LHRH and LHRH-R-I in the transitional cell carcinoma (TCC) type of human BC. RNA was extracted from 24 human bladder tumor specimens and three BC cell lines. RT-PCR was performed to detect mRNA for LHRH and LHRH-R-I. The protein of LHRH-R-I was further studied by immunohistochemistry (IHC), ligand competition assay, and Western Blot. PCR products of LHRH were found in 19 of 24 (79%) specimens and mRNA of LHRH-R-I was detected in 20 of 24 specimens (83%). Positive immunostaining for LHRH-R-I with different expression intensity was found in all samples examined, showing negative correlation with TCC grade. Radioligand binding studies also showed the presence of specific LHRH-R-I and high affinity binding of LHRH analogs. The high incidence of LHRH-R in BC suggests that it could serve as a molecular target for therapy of human BC with cytotoxic LHRH analogs or modern powerful antagonistic analogs of LHRH.

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Characterization of luteinizing hormone-releasing hormone receptor type I (LH-RH-I) as a potential molecular target in OCM-1 and OCM-3 human uveal melanoma cell lines

Cited by 5 publications

References 58 publications

The targeted LHRH analog AEZS-108 alters expression of genes related to angiogenesis and development of metastasis in uveal melanoma

The targeted LHRH analog AEZS-108 alters expression of genes related to angiogenesis and development of metastasis in uveal melanoma

Somatostatin Receptors as Molecular Targets in Human Uveal Melanoma

Expression of Luteinizing Hormone-Releasing Hormone (LHRH) and Type-I LHRH Receptor in Transitional Cell Carcinoma Type of Human Bladder Cancer

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