elib
DLR-Header
DLR-Logo -> http://www.dlr.de
DLR Portal Home | Imprint | Privacy Policy | Contact | Deutsch
Fontsize: [-] Text [+]

Differential Regulation of cGMP Signaling in Human Melanoma Cells at Altered Gravity: Simulated Microgravity Down-Regulates Cancer-Related Gene Expression and Motility

Ivanova, Krassimira and Eiermann, Peter and Tsiockas, Wasiliki and Hemmersbach, Ruth and Gerzer, Rupert (2018) Differential Regulation of cGMP Signaling in Human Melanoma Cells at Altered Gravity: Simulated Microgravity Down-Regulates Cancer-Related Gene Expression and Motility. Microgravity Science and Technology, 30 (4), pp. 457-467. Springer. DOI: 10.1007/s12217-018-9611-z ISSN 0938-0108

[img] PDF
1MB

Official URL: https://doi.org/10.1007/s12217-018-9611-z

Abstract

Altered gravity is known to affect cellular function by changes in gene expression and cellular signaling. The intracellular signaling molecule cyclic guanosine-3,5-monophosphate (cGMP), a product of guanylyl cyclases (GC), e.g., the nitric oxide (NO)-sensitive soluble GC (sGC) or natriuretic peptide-activated GC (GC-A/GC-B), is involved in melanocyte response to environmental stress. NO-sGC-cGMP signaling is operational in human melanocytes and non-metastatic melanoma cells, whereas up-regulated expression of GC-A/GC-B and inducible NO synthase (iNOS) are found in metastatic melanoma cells, the deadliest skin cancer. Here, we investigated the effects of altered gravity on the mRNA expression of NOS isoforms, sGC, GC-A/GC-B and multidrug resistance-associated proteins 4/5 (MRP4/MRP5) as selective cGMP exporters in human melanoma cells with different metastatic potential and pigmentation. A specific centrifuge (DLR, Cologne Germany) was used to generate hypergravity (5 g for 24 h) and a fast-rotating 2-D clinostat (60 rpm) to simulate microgravity values ≤0.012 g for 24 h. The results demonstrate that hypergravity up-regulates the endothelial NOS-sGCMRP4/MRP5 pathway in non-metastatic melanoma cells, but down-regulates it in simulated microgravity when compared to 1 g. Additionally, the suppression of sGC expression and activity has been suggested to correlate inversely to tumor aggressiveness. Finally, hypergravity is ineffective in highly metastatic melanoma cells, whereas simulated microgravity down-regulates predominantly the expression of the cancer-related genes iNOS and GC-A/GC-B (shown additionally on protein levels) as well as motility in comparison to 1 g. The results suggest that future studies in real microgravity can benefit from considering GC-cGMP signaling as possible factor for melanocyte transformation.

Item URL in elib:https://elib.dlr.de/120010/
Document Type:Article
Title:Differential Regulation of cGMP Signaling in Human Melanoma Cells at Altered Gravity: Simulated Microgravity Down-Regulates Cancer-Related Gene Expression and Motility
Authors:
AuthorsInstitution or Email of AuthorsAuthors ORCID iD
Ivanova, Krassimiragerman aerospace centre (dlr), institute of aerospace medicine, gravitational biology, cologne, germanyUNSPECIFIED
Eiermann, Petergerman aerospace centre (dlr), institute of aerospace medicine, gravitational biology, cologne, germanyUNSPECIFIED
Tsiockas, Wasilikigerman aerospace centre (dlr), institute of aerospace medicine, gravitational biology, cologne, germanyUNSPECIFIED
Hemmersbach, Ruthgerman aerospace centre (dlr), institute of aerospace medicine, gravitational biology, cologne, germanyhttps://orcid.org/0000-0001-5308-6715
Gerzer, RupertSpace Center, Skoltech University, Moscow, Russia.https://orcid.org/0000-0003-3845-8888
Date:29 March 2018
Journal or Publication Title:Microgravity Science and Technology
Refereed publication:Yes
Open Access:Yes
Gold Open Access:No
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:30
DOI :10.1007/s12217-018-9611-z
Page Range:pp. 457-467
Publisher:Springer
ISSN:0938-0108
Status:Published
Keywords:Guanylyl cyclase-cGMP signaling, Human melanoma cells, Hypergravity, Simulated microgravity, 2-D clinostat
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Forschung unter Weltraumbedingungen
DLR - Research theme (Project):R - Vorhaben Biowissenschaftliche Exp.-vorbereitung, R - Vorhaben Nutzerunterstützung Biowiss. Bodenprogramm
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Gravitational Biology
Deposited By: Duwe, Helmut
Deposited On:14 Aug 2018 09:57
Last Modified:23 Feb 2019 00:22

Repository Staff Only: item control page

Browse
Search
Help & Contact
Information
electronic library is running on EPrints 3.3.12
Copyright © 2008-2017 German Aerospace Center (DLR). All rights reserved.