MCM2 and Carbonic Anhydrase 9 Are Novel Potential Targets for Neuroblastoma Pharmacological Treatment

被引:9
作者
Garbati, Patrizia [1 ]
Barbieri, Raffaella [1 ,8 ]
Cangelosi, Davide [2 ,9 ]
Zanon, Carlo [3 ]
Costa, Delfina [1 ]
Eva, Alessandra [2 ]
Thellung, Stefano [4 ,5 ]
Calderoni, Matilde [6 ]
Baldini, Francesca [6 ]
Tonini, Gian Paolo [3 ]
Modesto, Paola [7 ]
Florio, Tullio [1 ,4 ,5 ]
Pagano, Aldo [1 ,6 ]
机构
[1] IRCCS Osped Policlin San Martino, I-16132 Genoa, Italy
[2] IRCCS Giannina Gaslini Inst, Lab Mol Biol, I-16147 Genoa, Italy
[3] Fdn Citta Speranza, Ist Ric Pediat IRP, Haematol Oncol Lab, I-35127 Padua, Italy
[4] Univ Genoa, Dept Internal Med, I-16132 Genoa, Italy
[5] Univ Genoa, Ctr Excellence Biomed Res, I-16132 Genoa, Italy
[6] Univ Genoa, Dept Expt Med, I-16132 Genoa, Italy
[7] Vet Med Res Inst Piemonte, Natl Reference Ctr Vet & Comparat Oncol, I-10154 Turin, Italy
[8] CNR, Biophys Inst, Via Marini 6, I-16149 Genoa, Italy
[9] IRCCS Giannina Gaslini Inst, Clin Bioinformat Unit, I-16147 Genoa, Italy
关键词
neuroblastoma; carbonic anhydrase 9; MCM2; ciprofloxacin; acetazolamide; CANCER; RNA; IX; GENE; ANGIOGENESIS; EXPRESSION; NDM29; PROLIFERATION; CIPROFLOXACIN; PERTURBATION;
D O I
10.3390/biomedicines8110471
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
To overcome the lack of effective pharmacological treatments for high-risk neuroblastoma (HR-NB), the development of novel in vitro and in vivo models that better recapitulate the disease is required. Here, we used an in vitro multiclonal cell model encompassing NB cell differentiation stages, to identify potential novel pharmacological targets. This model allowed us to identify, by low-density RT-PCR arrays, two gene sets, one over-expressed during NB cell differentiation, and the other up-regulated in more malignant cells. Challenging two HR-NB gene expression datasets, we found that these two gene sets are related to high and low survival, respectively. Using mouse NB cisplatin-treated xenografts, we identified two genes within the list associated to the malignant stage (MCM2 and carbonic anhydrase 9), whose expression is positively correlated with tumor growth. Thus, we tested their pharmacological targeting as potential therapeutic strategy. We measured mice survival and tumor growth rate after xenografts of human NB treated with cisplatin in the presence of MCM2/carbonic anhydrase 9 inhibitors (ciprofloxacin and acetazolamide). MCM2 or carbonic anhydrase 9 inhibition significantly increased cisplatin activity, supporting their possible testing for NB therapy.
引用
收藏
页码:1 / 19
页数:19
相关论文
共 51 条
[1]   Carbonic anhydrase inhibitors: E7070, a sulfonamide anticancer agent, potently inhibits cytosolic isozymes I and II, and transmembrane, tumor-associated isozyme IX [J].
Abbate, F ;
Casini, A ;
Owa, T ;
Scozzafava, A ;
Supuran, CT .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (01) :217-223
[2]   Generation of a Functional Human Neural Network by NDM29 Overexpression in Neuroblastoma Cancer Cells [J].
Alloisio, Susanna ;
Garbati, Patrizia ;
Viti, Federica ;
Dante, Silvia ;
Barbieri, Raffaella ;
Arnaldi, Giovanni ;
Petrelli, Alessia ;
Gigoni, Arianna ;
Giannoni, Paolo ;
Quarto, Rodolfo ;
Nobile, Mario ;
Vassalli, Massimo ;
Pagano, Aldo .
MOLECULAR NEUROBIOLOGY, 2017, 54 (08) :6097-6106
[3]   mRNA expression levels of hypoxia-induced and stem cell-associated genes in human glioblastoma [J].
Bache, Matthias ;
Rot, Swetlana ;
Kessler, Jacqueline ;
Guettler, Antje ;
Wichmann, Henri ;
Greither, Thomas ;
Wach, Sven ;
Taubert, Helge ;
Soeling, Ariane ;
Bilkenroth, Udo ;
Kappler, Matthias ;
Vordermark, Dirk .
ONCOLOGY REPORTS, 2015, 33 (06) :3155-3161
[4]   Circulating Carbonic Anhydrase IX and Antiangiogenic Therapy in Breast Cancer [J].
Brown-Glaberman, Ursa ;
Marron, Marilyn ;
Chalasani, Pavani ;
Livingston, Robert ;
Iannone, Maria ;
Specht, Jennifer ;
Stopeck, Alison T. .
DISEASE MARKERS, 2016, 2016
[5]   An Alu-like RNA promotes cell differentiation and reduces malignancy of human neuroblastoma cells [J].
Castelnuovo, Manuele ;
Massone, Sara ;
Tasso, Roberta ;
Fiorino, Gloria ;
Gatti, Monica ;
Robello, Mauro ;
Gatta, Elena ;
Berger, Audrey ;
Strub, Katharina ;
Florio, Tullio ;
Dieci, Giorgio ;
Cancedda, Ranieri ;
Pagano, Aldo .
FASEB JOURNAL, 2010, 24 (10) :4033-4046
[6]   Medicinal potential of ciprofloxacin and its derivatives [J].
Castro, William ;
Navarro, Maribel ;
Biot, Christophe .
FUTURE MEDICINAL CHEMISTRY, 2013, 5 (01) :81-96
[7]   Pathway Commons, a web resource for biological pathway data [J].
Cerami, Ethan G. ;
Gross, Benjamin E. ;
Demir, Emek ;
Rodchenkov, Igor ;
Babur, Oezguen ;
Anwar, Nadia ;
Schultz, Nikolaus ;
Bader, Gary D. ;
Sander, Chris .
NUCLEIC ACIDS RESEARCH, 2011, 39 :D685-D690
[8]   Selective Inhibition of Carbonic Anhydrase IX Decreases Cell Proliferation and Induces Ceramide-Mediated Apoptosis in Human Cancer Cells [J].
Cianchi, Fabio ;
Vinci, Maria Cristina ;
Supuran, Claudiu T. ;
Peruzzi, Benedetta ;
De Giuli, Paolo ;
Fasolis, Giuseppe ;
Perigli, Giuliano ;
Pastorekova, Silvia ;
Papucci, Laura ;
Pini, Alessandro ;
Masini, Emanuela ;
Puccetti, Luca .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2010, 334 (03) :710-719
[9]   An intronic ncRNA-dependent regulation of SORL1 expression affecting Aβ formation is upregulated in post-mortem Alzheimer's disease brain samples [J].
Ciarlo, Eleonora ;
Massone, Sara ;
Penna, Ilaria ;
Nizzari, Mario ;
Gigoni, Arianna ;
Dieci, Giorgio ;
Russo, Claudio ;
Florio, Tullio ;
Cancedda, Ranieri ;
Pagano, Aldo .
DISEASE MODELS & MECHANISMS, 2013, 6 (02) :424-433
[10]   Carbonic anhydrase IX: Biochemical and crystallographic characterization of a novel antitumor target [J].
De Simone, Giuseppina ;
Supuran, Claudiu T. .
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, 2010, 1804 (02) :404-409