Modeled microgravity suppressed invasion and migration of human glioblastoma U87 cells through downregulating store-operated calcium entry

Shi, Zixuan; Rao, Wei; Wang, Huan; Wang, Nanding; Si, Jingwen; Zhao, Jiao; Li, Junchang; Wang, Zongren

doi:10.1016/j.bbrc.2014.12.120

Cited by 35 publications

(30 citation statements)

References 28 publications

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“…Importantly, as shown in our previous studies (Ivanova et al 2011) and verified here additionally on protein level, simulated microgravity induces down-regulation of the expression of both ANP-responsible GC-A and CNPresponsible GC-B in the investigated metastatic melanoma cells in comparison to 1-g controls. Moreover, our current data indicate a reduction in the motility of clinorotated highly metastatic BLM melanoma cells in comparison to 1-g control cells, which is in agreement with a reported reduction of migration for human lung adenocarcinoma cell line (Chang et al 2013) as well as for human glioblastoma U87 cells during clinorotation (Shi et al 2015). In addition, very recent report shows that the ability of fibroblasts to migrate was significantly impaired at modeled microgravity conditions using a Rotary cell culture system (Cialdai et al 2017).…”

Section: Discussionsupporting

confidence: 92%

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

Ivanova

Eiermann

Tsiockas

et al. 2018

Microgravity Sci. Technol.

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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-sGC-MRP4/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.

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Section: Discussionsupporting

confidence: 92%

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

Ivanova

Eiermann

Tsiockas

et al. 2018

Microgravity Sci. Technol.

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“…Binding of integrins to matrix proteins promotes the bundling of F-actin at the cell-matrix adhesion and the subsequent maturation of both the focal adhesion and the actin stress fiber (Zaidel-Bar et al, 2003;Wolfenson et al, 2009Wolfenson et al, , 2011 to generate the tension required for cell adherence, migration, and tissue homeostasis. Exposure to microgravity reduces the formation, number, and total area of focal adhesions per cell (Guignandon et al, 2003;Tan et al, 2018) consequently affecting cellular adherence, migration capacity, and viability (Plett et al, 2004;Nabavi et al, 2011;Shi et al, 2015;Ahn et al, 2019;Dietz et al, 2019), albeit with contradictory results. Mechanical unloading has been shown to significantly reduce gene expression of a number of focal adhesion proteins, including FAK, DOCK1, and PTEN, while caveolin and p130Cas expression were shown to be increased (Grenon et al, 2013;Ratushnyy and Buravkova, 2017).…”

Section: The Impact Of Microgravity Of Cell Cytoskeletonmentioning

confidence: 99%

“…When applied to tumor cells microgravity has been found to impact tumor cell adhesion, proliferation, migration, and viability (Grimm et al, 2002;Plett et al, 2004;Infanger et al, 2006a;Shi et al, 2015;Tan et al, 2018), and to induce cell autophagy (Jeong et al, 2018). Changes in apoptotic rate were also observed in colorectal cancer cells (DLD-1) and a lymphoblast leukemic cell line (MOLT-4), accompanied by reduced transcription of the genes involved in colony formation, oncogenic progression, and metastatic potential (Vidyasekar et al, 2015).…”

Section: Microgravity-induced Cytoskeletal Regulation Of Immune and Cmentioning

confidence: 99%

Modeling the Impact of Microgravity at the Cellular Level: Implications for Human Disease

Bradbury

Choi

et al. 2020

Front. Cell Dev. Biol.

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A lack of gravity experienced during space flight has been shown to have profound effects on human physiology including muscle atrophy, reductions in bone density and immune function, and endocrine disorders. At present, these physiological changes present major obstacles to long-term space missions. What is not clear is which pathophysiological disruptions reflect changes at the cellular level versus changes that occur due to the impact of weightlessness on the entire body. This review focuses on current research investigating the impact of microgravity at the cellular level including cellular morphology, proliferation, and adhesion. As direct research in space is currently cost prohibitive, we describe here the use of microgravity simulators for studies at the cellular level. Such instruments provide valuable tools for cost-effective research to better discern the impact of weightlessness on cellular function. Despite recent advances in understanding the relationship between extracellular forces and cell behavior, very little is understood about cellular biology and mechanotransduction under microgravity conditions. This review will examine recent insights into the impact of simulated microgravity on cell biology and how this technology may provide new insight into advancing our understanding of mechanically driven biology and disease.

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“…In addition, a reduction in the migration has also been reported for a human adenocarcinoma cell line [90] and human glioblastoma U87 cells during clinorotation (30 rpm) [91] as well as an impaired ability of fibroblasts to migrate in "a modeled microgravity conditions" using a RWV [92]. Moreover, it was reported that random positioning on a three-dimensional clinostat (with 30 • /s angular velocity) reduced BL6-10 melanoma cell proliferation, adhesion, and invasiveness in vitro and decreased tumor lung metastasis in vivo via FAK/RhoA-regulated mTORC1 and AMP-activated protein kinase pathways [93].…”

Section: Effects Of Altered Gravity In Metastatic Melanoma Cellsmentioning

confidence: 71%

Guanylyl Cyclase-cGMP Signaling Pathway in Melanocytes: Differential Effects of Altered Gravity in Non-Metastatic and Metastatic Cells

Ivanova

Hemmersbach

2020

IJMS

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Human epidermal melanocytes as melanin producing skin cells represent a crucial barrier against UV-radiation and oxidative stress. It was shown that the intracellular signaling molecule cyclic guanosine-3 ,5 -monophosphate (cGMP), generated by the guanylyl cyclases (GCs), e.g., the nitric oxide (NO)-sensitive soluble GC (sGC) and the natriuretic peptide-activated particulate GC (GC-A/GC-B), plays a role in the melanocyte response to environmental stress. Importantly, cGMP is involved in NO-induced perturbation of melanocyte-extracellular matrix interactions and in addition, increased NO production during inflammation may lead to loss of melanocytes and support melanoma metastasis. Further, the NO-sensitive sGC is expressed predominantly in human melanocytes and non-metastatic melanoma cells, whereas absence of functional sGC but up-regulated expression of GC-A/GC-B and inducible NO synthase (iNOS) are detected in metastatic cells. Thus, suppression of sGC expression as well as up-regulated expression of GC-A/GC-B/iNOS appears to correlate with tumor aggressiveness. As the cGMP pathway plays important roles in melanocyte (patho)physiology, we present an overview on the differential effects of altered gravity (hypergravity/simulated microgravity) on the cGMP signaling pathway in melanocytes and melanoma cells with different metastatic potential. We believe that future experiments in real microgravity may benefit from considering cGMP signaling as a possible factor for melanocyte transformation and in medication.

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Modeled microgravity suppressed invasion and migration of human glioblastoma U87 cells through downregulating store-operated calcium entry

Cited by 35 publications

References 28 publications

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

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

Modeling the Impact of Microgravity at the Cellular Level: Implications for Human Disease

Guanylyl Cyclase-cGMP Signaling Pathway in Melanocytes: Differential Effects of Altered Gravity in Non-Metastatic and Metastatic Cells

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