scholarly journals miR-638 promotes melanoma metastasis and protects melanoma cells from apoptosis and autophagy

Oncotarget ◽  
2014 ◽  
Vol 6 (5) ◽  
pp. 2966-2980 ◽  
Author(s):  
Animesh Bhattacharya ◽  
Ulf Schmitz ◽  
Yvonne Raatz ◽  
Madeleine Schönherr ◽  
Tina Kottek ◽  
...  
Keyword(s):  
Melanoma Cells ◽  
Melanoma Metastasis

scholarly journals Natural products with therapeutic potential in melanoma metastasis

2015 ◽  
Vol 32 (8) ◽  
pp. 1170-1182 ◽  
Author(s):  
A. AlQathama ◽  
J. M. Prieto
Keyword(s):  
Natural Products ◽  
Cancer Treatment ◽  
Therapeutic Potential ◽  
Melanoma Cells ◽  
Mechanisms Of Action ◽  
Melanoma Metastasis ◽  
Pharmacological Effects ◽  
Cytotoxic Compounds

Natural products continue to provide lead cytotoxic compounds for cancer treatment but less attention has been given to antimigratory compounds. We here systematically and critically survey more than 30 natural products with direct in vitro and in vivo pharmacological effects on migration and/or metastasis of melanoma cells and chart the mechanisms of action for this underexploited property.

Differentiation between Melanin-Laden Macrophages and Melanoma Cells in Vitreous Aspirates

2016 ◽  
Vol 60 (1) ◽  
pp. 25-30
Author(s):  
Ernest Iakovlev ◽  
Zeina Ghorab ◽  
Hatem Krema ◽  
Vladimir Iakovlev ◽  
Peter Kertes ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Retinal Detachment ◽  
Melanoma Cells ◽  
Melanoma Metastasis ◽  
Vitreous Fluid ◽  
Diagnostic Features ◽  
Pigmented Lesions ◽  
Atypical Cells ◽  
History Of ◽  
A Current

Objective: The differential diagnosis between retinal detachment and melanoma metastatic to the vitreous can be challenging, both clinically and cytologically. We demonstrate the diagnostic features and pitfalls of the cytological assessment. Study Design: A case of a metastatic melanoma to the vitreous is compared to a case of retinal detachment initially suspected as melanoma metastasis. Case 1 was a 54-year-old patient with a vague history of pigmented lesions 20 years previously and a current presentation of a visual defect. Case 2 was a 68-year-old patient with a history of melanoma and a presentation of floaters and flashing lights. Results: The vitreous fluid of case 1 contained atypical, pigment-laden cells positive for HMB-45 and assessed as melanoma. On enucleation, a melanoma metastatic to the vitreous was diagnosed. The vitreous fluid of case 2 revealed atypical cells containing pigment granules. The cells were negative for melanocytic markers, while the granules stained positive for melanin. Macrophage marker CD163 was positive in all cells. The interpretation was one of macrophages reactive to the retinal detachment. Conclusion: Melanin-laden macrophages can mimic melanoma cells. This needs to be considered in the differential diagnosis. Additional stains can help the distinction.

Newmouse models of melanoma metastasis and differences in brain tropism and metastatic growth pattern.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19015-e19015
Author(s):  
Amr M. Morsi ◽  
Avital Gazial-Sovran ◽  
Hana Baig ◽  
Robert S. Kerbel ◽  
John Golfinos ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Ex Vivo ◽  
Three Dimensional ◽  
Melanoma Cells ◽  
Melanoma Metastasis ◽  
Optimal Method ◽  
In Vivo Models ◽  
Dismal Prognosis ◽  
Intracardiac Injection

e19015 Background: 75% of patients with metastatic melanoma develop brain metastases (B-mets). Such patients show dismal prognosis with a median survival of < 6 months. Scarcity of clinically relevant in vivo models has hindered melanoma B-met studies. We compared the in vivo dissemination upon ultrasound (u/s) guided intracardiac injection of B16F10 cells to 131/4-5B1 (hereafter 5B1), a WM239A subclone with enhanced brain tropism. We also implemented an ex vivo MRI protocol as a high throughput three dimensional approach for characterizing B-mets penetrance and growth. Methods: B16-F10 or 5B1 melanoma cells were injected in C57BL/6J mice (n=40) or athymic/nude mice (n=40) respectively using u/s-guided intracardiac injection. Upon weight loss, mice were euthanized, and heads prepared for ex vivo imaging. All µMRI experiments were performed with a 7T Bruker Avance II console. The protocol consisted of (110-mm)3 isotropic T1-, T2- and T2*-weighted sequences. Results: Our ex vivo MRI recapitulates the clinical radiological T1 and T2 brightening as well as susceptibility-induced T2* darkening effect of melanoma. The B16F10 model revealed exclusive ventricular and leptomeningeal spread while the 5B1 model showed parenchymal lesions. In addition, 90% of the 5B1 mice with brain tumors showed multiple lesions (3-16) vs. 18% in the B16F10 model (1- 3). Finally, 3D volume studies revealed a higher B-met penetrance (68% vs. 18%), delayed onset of tumor detection (earliest-day 27 vs. day 15) post-injection and a slower growth rate of 5B1 brain metastases compared to B16F10 tumors. Conclusions: Our results suggest that u/s-guided intracardiac injection of melanoma cells is an optimal method to capture the cells’ spontaneous dissemination pattern (or site-specific tropism) and that the 5B1 model is a more clinically relevant model of melanoma B-met for preclinical studies.

scholarly journals Identification of core genes and pathways in melanoma metastasis via bioinformatics analysis

2020 ◽  
Author(s):  
Yumei Li ◽  
Bifei Li ◽  
Fan Chen ◽  
Weiyu Shen ◽  
Vladimir L. Katanaev ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metastatic Melanoma ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Primary Melanoma ◽  
Melanoma Cells ◽  
Receptor Interaction ◽  
Melanoma Metastasis ◽  
Hub Genes ◽  
Core Genes

Abstract Background Metastasis is the leading cause of melanoma mortality. Current therapies are rarely curative for metastatic melanoma, revealing the urgent need to identify more effective preventive and therapeutic targets. This study aimed to screen for the key core genes and molecular mechanisms related to the metastasis of melanoma. Methods Gene expression profile, GSE8401 including 31 primary melanoma and 52 metastatic melanoma clinical samples, was downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between metastatic melanoma and primary melanoma were screened using GEO2R. Assays of gene ontology (GO), Kyoto Encyclopedia of Gene and Genome (KEGG) pathway and protein-protein interaction (PPI) were performed to visualize these DEGs through Database for Annotation, Visualization and Integrated Discovery (DAVID) software and Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape with Molecular Complex Detection (MCODE) plug-in tools. Top 10 genes with high degree were defined as hub genes. Furthermore, paired post-metastatic melanoma cells and pre-metastatic melanoma cells were established by experimental mouse model of melanoma metastasis to verify the expression of these hub genes. Results 424 DEGs between the metastatic melanoma and primary melanoma were screened, including 60 upregulated genes enriched in ECM-receptor interaction and progesterone-mediated oocyte maturation and 364 downregulated genes enriched in amoebiasis, melanogenesis, and ECM-receptor interaction. CDH1, EGFR, KRT5, COL17A1, KRT14, IVL, DSP, DSG1, FLG and CDK1 were defined as the hub genes. . In addition, paired post-metastatic melanoma cells (A375M) and pre-metastatic melanoma cells (A375) were established and qRT-PCR analysis confirmed the expression of the hub genes during melanoma metastasis. Conclusion This bioinformatic study has provided a deeper understanding of the molecular mechanisms of melanoma metastasis. KRT5, IVL and COL17A1 have emerged as possible biomarkers and therapeutic targets in metastasis of melanoma.

scholarly journals Low-Dose Albendazole Inhibits Epithelial-Mesenchymal Transition of Melanoma Cells by Enhancing Phosphorylated GSK-3β/Tyr216 Accumulation

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Zhiqiang He ◽  
Shun Lei ◽  
Fucheng Liang ◽  
Liuchang Tan ◽  
Weinan Zhang ◽  
...  
Keyword(s):  
Low Dose ◽  
Epithelial Mesenchymal Transition ◽  
Inhibitory Effect ◽  
Melanoma Cells ◽  
Melanoma Metastasis ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Mesenchymal Transition ◽  
Phosphorylated Akt ◽  
Gsk 3Β

Albendazole (ABZ) is an effective broad-spectrum anthelmintic agent that has been widely used for humans and animals. Previous studies have reported that ABZ exhibits antitumor effects against melanoma and other different cancer types; however, it is unknown whether ABZ exerts the inhibitory effect against melanoma metastasis. In this study, we aimed to investigate the inhibitory effect of ABZ on melanoma cells. Through in vitro studies, we discovered that low-dose ABZ treatment significantly inhibited the migration and invasion, but not the proliferation, of A375 and B16-F10 cells in a dose-dependent manner. Further analysis revealed that ABZ treatment reduced the expression level of snail family transcriptional repressor 1 (Snail) in the cytoplasm and nucleus by decreasing the levels of phosphorylated AKT (pAKT) Ser473/GSK-3β (pGSK-3β) Ser9 and increasing pGSK-3β/Tyr216, resulting in a significant upregulation of E-cadherin and downregulation of N-cadherin and ultimately reversing the epithelial-mesenchymal transition (EMT) process of melanoma cells. In contrast, the continuous activation of AKT via transfected plasmids elevated the protein levels of pAKT Ser473/pGSK-3β Ser9 and Snail and antagonized the inhibitory action of ABZ. We also confirmed that ABZ treatment effectively inhibited the lung metastasis of melanoma in nude mice in vivo. Subsequent immunohistochemical analysis verified the decreased pAKT Ser473/pGSK-3β Ser9 and increased pGSK-3β/Tyr216 levels in ABZ-treated subcutaneous tumors. Therefore, our findings demonstrate that ABZ treatment can suppress the EMT progress of melanoma by increasing the pGSK-3β/Tyr216-mediated degradation of Snail, which may be used as a potential treatment strategy for metastatic melanoma.

scholarly journals Lymphatic endothelium stimulates melanoma metastasis and invasion via MMP14-dependent Notch3 and β1-integrin activation

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Pirita Pekkonen ◽  
Sanni Alve ◽  
Giuseppe Balistreri ◽  
Silvia Gramolelli ◽  
Olga Tatti-Bugaeva ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Melanoma Cells ◽  
Lymphatic Invasion ◽  
Cell Phenotype ◽  
Melanoma Metastasis ◽  
Β1 Integrin ◽  
Integrin Activation ◽  
Primary Tumors ◽  
Distant Organ Metastasis ◽  
3D Matrix

Lymphatic invasion and lymph node metastasis correlate with poor clinical outcome in melanoma. However, the mechanisms of lymphatic dissemination in distant metastasis remain incompletely understood. We show here that exposure of expansively growing human WM852 melanoma cells, but not singly invasive Bowes cells, to lymphatic endothelial cells (LEC) in 3D co-culture facilitates melanoma distant organ metastasis in mice. To dissect the underlying molecular mechanisms, we established LEC co-cultures with different melanoma cells originating from primary tumors or metastases. Notably, the expansively growing metastatic melanoma cells adopted an invasively sprouting phenotype in 3D matrix that was dependent on MMP14, Notch3 and β1-integrin. Unexpectedly, MMP14 was necessary for LEC-induced Notch3 induction and coincident β1-integrin activation. Moreover, MMP14 and Notch3 were required for LEC-mediated metastasis of zebrafish xenografts. This study uncovers a unique mechanism whereby LEC contact promotes melanoma metastasis by inducing a reversible switch from 3D growth to invasively sprouting cell phenotype.

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

2020 ◽  
Vol 21 (3) ◽  
pp. 1139 ◽  
Author(s):  
Krassimira Ivanova ◽  
Ruth Hemmersbach
Keyword(s):  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Melanoma Cells ◽  
No Production ◽  
Melanoma Metastasis ◽  
Altered Gravity ◽  
Differential Effects ◽  
Metastatic Cells ◽  
Regulated Expression ◽  
Cgmp Signaling

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.

scholarly journals Xanthohumol, a Prenylated Chalcone Derived from Hops, Inhibits Growth and Metastasis of Melanoma Cells

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 511
Author(s):  
Tatjana Seitz ◽  
Christina Hackl ◽  
Kim Freese ◽  
Peter Dietrich ◽  
Abdo Mahli ◽  
...  
Keyword(s):  
Hepatic Metastasis ◽  
Dose Range ◽  
Melanoma Cells ◽  
In Vivo Studies ◽  
Melanoma Metastasis ◽  
Anticancer Activities ◽  
Prenylated Chalcone ◽  
The Impact

Melanoma is one of the most aggressive and lethal cancers worldwide. Despite recent progress in melanoma therapy, the prognosis for metastasized melanoma continues to be poor. Xanthohumol (XN), a prenylated chalcone derived from hop cones, is known to possess a broad spectrum of chemopreventive and anticancer activities. However, few studies have analyzed functional XN effects on melanoma cells and there have been no previous in vivo studies of its effects on metastasis. The aim of this study was to investigate the impact of XN on the tumorigenic and liver metastatic activity of melanoma cells. XN exhibited dose-dependent cytotoxic effects on human melanoma cell lines (Mel Ju; Mel Im) in vitro. Functional analysis in the subtoxic dose-range revealed that XN dose-dependently inhibited proliferation, colony formation, and migratory activity of melanoma cells. Subtoxic XN doses also induced markers of endoplasmic reticulum stress but inhibited the phosphorylation of the protumorigenic c-Jun N-terminal kinases (JNK). Furthermore, XN effects on hepatic metastasis were analyzed in a syngeneic murine model (splenic injection of murine B16 melanoma cells in C57/BL6 mice). Here, XN significantly reduced the formation of hepatic metastasis. Metastases formed in the liver of XN-treated mice revealed significantly larger areas of central necrosis and lower Ki67 expression scores compared to that of control mice. In conclusion, XN inhibits tumorigenicity of melanoma cells in vitro and significantly reduced hepatic metastasis of melanoma cells in mice. These data, in conjunction with an excellent safety profile that has been confirmed in previous studies, indicate XN as a promising novel agent for the treatment of hepatic (melanoma) metastasis.

scholarly journals NecroX-5 Can Suppress Melanoma Metastasis by Reducing the Expression of Rho-Family GTPases

2021 ◽  
Vol 10 (13) ◽  
pp. 2790
Author(s):  
Gue-Tae Moon ◽  
Ji-Hyun Lee ◽  
Sang-Hyun Jeong ◽  
Song-Wan Jin ◽  
Young-Min Park
Keyword(s):  
Cell Lines ◽  
Melanoma Cell ◽  
Cancer Metastasis ◽  
Melanoma Cells ◽  
Untreated Group ◽  
Melanoma Metastasis ◽  
Rho Family Gtpases ◽  
Melanoma Model ◽  
Rho Family ◽  
Melanoma Cell Lines

NecroX-5 (NX-5) is a cell-permeable necrosis inhibitor with cytoprotective effects. Although it has been reported to inhibit lung and breast cancer metastasis by modulating migration, its therapeutic effect on melanoma metastasis is still unknown. In this study, we examined the anti-metastatic effect of NX-5 on melanoma cell lines and its related therapeutic mechanism. The anti-metastatic effect of NX-5 on melanoma cell lines was determined using a transwell migration assay. We performed a quantitative real-time polymerase chain reaction and western blot analysis to measure changes in the expression of mRNA and protein, respectively, for major mediators of Rho-family GTPases after NX-5 treatment in melanoma cells. In addition, after constructing the 3D melanoma model, the expression of Rho-family GTPases was measured by immunohistochemistry. NX-5 (10 μM and 20 μM) treatment significantly reduced melanoma cell migration (p < 0.01). Additionally, NX-5 (20 μM) treatment significantly decreased the mRNA and protein expression levels of Cdc42, Rac1, and RhoA in melanoma cells compared with the untreated group (p < 0.001 and p < 0.05, respectively). Immunohistochemistry for our 3D melanoma model showed that Cdc42, Rac1, and RhoA were constitutively expressed in the nuclei of melanoma cells of the untreated group, and NX-5 treatment decreased their expression. These results demonstrate that NX-5 can suppress melanoma metastasis by reducing the expression of Rho-family GTPases.

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