Genomic profiling of invasive melanoma cell lines by array comparative genomic hybridization

Koroknai, Viktória; Ecsedi, Szilvia; Vízkeleti, Laura; Kiss, Tímea; Szász, István; Lukacs, A.; Papp, Orsolya; Ádány, Róza; Balázs, Margit

doi:10.1097/cmr.0000000000000227

Cited by 10 publications

(7 citation statements)

References 54 publications

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“…The invasive potential of the inhibitor (ENCO+BINI)-sensitive and -resistant melanoma cells was evaluated using BioCoat Matrigel Invasion Chambers (BD Biosciences, Bedford, MA, USA) as described before [ 13 ]. Shortly, for BRAFi/MEKi-sensitive cells, the upper part of the invasion chamber was filled with a serum-free cell suspension (500 µL), and growth medium with 10% FBS was used (as a chemoattractant) in the lower chamber.…”

Section: Methodsmentioning

confidence: 99%

Molecular Alterations Associated with Acquired Drug Resistance during Combined Treatment with Encorafenib and Binimetinib in Melanoma Cell Lines

Patel

Szász

Koroknai

et al. 2021

Cancers

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Combination treatment using BRAF/MEK inhibitors is a promising therapy for patients with advanced BRAFV600E/K mutant melanoma. However, acquired resistance largely limits the clinical efficacy of this drug combination. Identifying resistance mechanisms is essential to reach long-term, durable responses. During this study, we developed six melanoma cell lines with acquired resistance for BRAFi/MEKi treatment and defined the molecular alterations associated with drug resistance. We observed that the invasion of three resistant cell lines increased significantly compared to the sensitive cells. RNA-sequencing analysis revealed differentially expressed genes that were functionally linked to a variety of biological functions including epithelial-mesenchymal transition, the ROS pathway, and KRAS-signalling. Using proteome profiler array, several differentially expressed proteins were detected, which clustered into a unique pattern. Galectin showed increased expression in four resistant cell lines, being the highest in the WM1617E+BRes cells. We also observed that the resistant cells behaved differently after the withdrawal of the inhibitors, five were not drug addicted at all and did not exhibit significantly increased lethality; however, the viability of one resistant cell line (WM1617E+BRes) decreased significantly. We have selected three resistant cell lines to investigate the protein expression changes after drug withdrawal. The expression patterns of CapG, Enolase 2, and osteopontin were similar in the resistant cells after ten days of “drug holiday”, but the Snail protein was only expressed in the WM1617E+BRes cells, which showed a drug-dependent phenotype, and this might be associated with drug addiction. Our results highlight that melanoma cells use several types of resistance mechanisms involving the altered expression of different proteins to bypass drug treatment.

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Section: Methodsmentioning

confidence: 99%

Molecular Alterations Associated with Acquired Drug Resistance during Combined Treatment with Encorafenib and Binimetinib in Melanoma Cell Lines

Patel

Szász

Koroknai

et al. 2021

Cancers

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“…The invasive potential of the melanoma cell lines was analyzed using BD Biocoat Matrigel invasion chambers (pore size: 8 μm, 24-well; BD Biosciences, Bedford, Massachusetts, United States) as described by Koroknai et al [29] . The upper chamber of the insert was filled with 500 μL of cell suspension in serum-free media (5 × 10 4 cells/well).…”

Section: Methodsmentioning

confidence: 99%

Silencing Osteopontin Expression Inhibits Proliferation, Invasion and Induce Altered Protein Expression in Melanoma Cells

Kiss

Jámbor

Koroknai

et al. 2021

Pathol. Oncol. Res.

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Osteopontin (OPN) is a multifunctional phosphoprotein that is expressed in different types of cancers, including melanoma. OPN overexpression is associated with tumor progression and metastasis formation; however, the role of OPN in cell invasion and metastasis formation is not completely understood. In this study we aimed to define OPN expression in melanoma tissues and cell lines and investigate the effect of OPN expression on cell proliferation and invasion after inhibiting OPN expression with small interfering RNA (siRNA). OPN gene expression was determined by qRT-PCR, while protein expression was examined using a Proteome Profiler Oncology Array. siRNA-mediated OPN knockdown led to decreased OPN expression in melanoma cell lines, which was associated with decreased cell proliferation and invasion. Proteome profile analysis revealed significantly different protein expression between the original and transfected cell lines. The altered expression of the differently expressed proteins was validated at the mRNA level. Furthermore, OPN-specific siRNA was able to reduce OPN expression and inhibit the invasiveness of melanoma cells. Our results revealed for the first time that silencing the OPN gene influences proliferation and invasion of melanoma cells by effecting EGFR, tenascin C, survivin, galectin-3 and enolase 2 expression. To predict protein-protein interactions along with putative pathways we used STRING analysis for the differentially expressed proteins. These proteins formed multiple clusters, including extracellular matrix organization, regulation of angiogenesis, cell death and cell migration, PI3K-Akt, MAPK and focal adhesion signaling pathways. Taken together these data suggest that OPN might be an ideal target for drug development and therapies.

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“…Conversely, in mammary carcinoma, RET and GFRα1 are highly regulated by estrogen, and significant cross talk exists between the pathways (see below) [152] , [153] , [154] . Genomic profiling of invasive melanoma found that GDNF was one of the genes that were highly amplified in invasive cell lines as compared to noninvasive ones, suggesting an important function in the melanoma metastasis [155] .…”

Section: The Physiological Role Of Gflsmentioning

confidence: 99%

The GDNF Family: A Role in Cancer?

et al. 2018

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The glial cell line–derived neurotrophic factor (GDNF) family of ligands (GFLs) comprising of GDNF, neurturin, artemin, and persephin plays an important role in the development and maintenance of the central and peripheral nervous system, renal morphogenesis, and spermatogenesis. Here we review our current understanding of GFL biology, and supported by recent progress in the area, we examine their emerging role in endocrine-related and other non–hormone-dependent solid neoplasms. The ability of GFLs to elicit actions that resemble those perturbed in an oncogenic phenotype, alongside mounting evidence of GFL involvement in tumor progression, presents novel opportunities for therapeutic intervention.

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Genomic profiling of invasive melanoma cell lines by array comparative genomic hybridization

Cited by 10 publications

References 54 publications

Molecular Alterations Associated with Acquired Drug Resistance during Combined Treatment with Encorafenib and Binimetinib in Melanoma Cell Lines

Molecular Alterations Associated with Acquired Drug Resistance during Combined Treatment with Encorafenib and Binimetinib in Melanoma Cell Lines

Silencing Osteopontin Expression Inhibits Proliferation, Invasion and Induce Altered Protein Expression in Melanoma Cells

The GDNF Family: A Role in Cancer?

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