Lower Levels of Adiponectin and Its Receptor Adipor1 in the Uveal Melanomas With Monosomy-3
| Autor: | Salvatore Grisanti, Vinodh Kakkassery, Huaxin Zuo, Mahdy Ranjbar, Christiane Thieme, Anton Brosig, Siranush Vardanyan, Hartmut Merz, Aysegül Tura, Tjorge Maassen |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Uveal Neoplasms tumor dormancy Immunocytochemistry Biology 03 medical and health sciences 0302 clinical medicine Adenosine Triphosphate Monosomy monosomy-3 insulin resistance Gene expression medicine Humans Neoplasm Metastasis Receptor nucleoli Melanoma Aged Adiponectin adiponectin General Medicine medicine.disease Neoplastic Cells Circulating Immunohistochemistry G2 Phase Cell Cycle Checkpoints 030104 developmental biology Ki-67 Antigen Cell culture 030220 oncology & carcinogenesis circulating melanoma cells (CMC) Cancer research Female Anatomy and Pathology/Oncology Chromosomes Human Pair 3 uveal melanoma Receptors Adiponectin Adipor1 Hormone |
| Zdroj: | Investigative Ophthalmology & Visual Science |
| ISSN: | 1552-5783 0146-0404 |
| Popis: | Purpose Adiponectin is an insulin-sensitizing and anticarcinogenic hormone that is encoded by a gene on chromosome 3. Here, we analyzed the expression of adiponectin and its receptor Adipor1 in primary uveal melanoma (UM) with regard to the monosomy-3 status and clinical factors, as well as the physiological response of UM cells to adiponectin. Methods Immunohistochemistry was performed on the primary UM of 34 patients. Circulating melanoma cells (CMC) were isolated by immunomagnetic enrichment. Monosomy-3 was evaluated by Immuno-FISH. Gene expression was analyzed using the RNAseq data of The Cancer Genome Atlas study. Cultures of choroidal melanocytes and UM were established from the samples of two patients. The proliferative potential of the UM cell lines Mel-270 and OMM-2.5 was determined by immunocytochemistry, immunoblotting, cell cycle analysis, nucleolar staining, and adenosine triphosphate (ATP) levels. Results UM with monosomy-3 exhibited a lower immunoreactivity for adiponectin and Adipor1, which was associated with monosomy-3-positive CMC and the development of extraocular growth or metastases. Both proteins were more abundant in the irradiated tumors and present in the cultured cells. Gene expression profile indicated the impairment of adiponectin-mediated signaling in the monosomy-3 tumors. Adiponectin induced a significant decline in the ATP levels, Ki-67 expression, cells in the G2/M phase, and nucleolar integrity in UM cultures. Conclusions Adiponectin deficiency appears to enhance the metastatic potential of the UM cells with monosomy-3 and the termination of tumor dormancy. Counteracting insulin resistance and improving the serum adiponectin levels might therefore be a valuable approach to prevent or delay the UM metastases. |
| Databáze: | OpenAIRE |
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