title: Inhibitor of vasculogenic mimicry restores sensitivity of resistant melanoma cells to DNA-damaging agents.
abstract: The increasing incidence of melanoma makes this cancer an important public health problem. Therapeutic resistance is still a major obstacle to the therapy of patients with metastatic melanomas. The aim of this study was to develop the melanoma cell line resistant to DNA-alkylating agents and to elucidate the mechanisms involved in acquired drug resistance. We established a unique melanoma subline Mel MeR resistant to DNA-alkylating drug aranoza by continuous stepwise selection of the Mel Me/WT cell line with increasing concentrations of this drug. Mel MeR cells were also cross-resistant to streptozotocin or cisplatin. Here, we show that aranoza-resistant melanoma cells modulate the ABC transporter activity, upregulate the expression of PRAME, adopt a vascular-related phenotype and engage in vasculogenic mimicry. LCS1269, a vasculogenic mimicry low-molecular-weight inhibitor, reverses the sensitivity of resistant melanoma cells to DNA-damaging agents. In this study, we provide experimental evidence that LCS1269 might be considered as a new potential anticancer agent capable of overcoming multidrug resistance for DNA-damaging agents in melanoma.
authors: Department of Experimental Diagnosis and Therapy of Tumors, N.N. Blokhin Russian Cancer Research Center, Moscow, Russia.
authors: Amalia
authors: A
authors: Vartanian
authors: Maria
authors: M
authors: Baryshnikova
authors: Olga
authors: O
authors: Burova
authors: Dariya
authors: D
authors: Afanasyeva
authors: Vsevolod
authors: V
authors: Misyurin
authors: Alexander
authors: A
authors: Belyаvsky
authors: Zoya
authors: Z
authors: Shprakh
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000235:genetics; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051927:CD24 Antigen / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D000071063:Endoglin / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006027:Glycosides / Q000494:pharmacology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D008770:Methylnitrosourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D010749:Phosphoprotein Phosphatases / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D020112:Rhodamine 123 / Q000378:metabolism; D060149:Tetraspanin 30 / Q000378:metabolism
chemical_list: C480744:ABCB5 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000951:Antigens, Neoplasm; D018906:Antineoplastic Agents, Alkylating; D051927:CD24 Antigen; C497889:CD24 protein, human; C497483:CD44 protein, human; C554586:CD63 protein, human; D002227:Carbazoles; C064206:ENG protein, human; D000071063:Endoglin; D005456:Fluorescent Dyes; C095365:GAGE1 protein, human; D006027:Glycosides; D018960:Hyaluronan Receptors; C000626357:LCS1269; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C404944:PRAME protein, human; D060149:Tetraspanin 30; C447099:aranoza; D018799:Intercellular Adhesion Molecule-1; D020112:Rhodamine 123; D008770:Methylnitrosourea; D019009:Proto-Oncogene Proteins c-kit; C413483:CTDSP1 protein, human; D010749:Phosphoprotein Phosphatases