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Involvement of A3 Adenosine Receptor in Neuroblastoma Progression via Modulation of the Hypoxic/Angiogenic Pathway
Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. The clinical course may range from spontaneous regression towards ganglioneuroblastoma/ganglioneuroma or maturation to a very aggressive form characterized by an extensive hypoxic area. In solid tumors, extracellular microe...
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| Published in: | Journal of molecular neuroscience 2019-09, Vol.69 (1), p.166-176 |
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| creator | Maugeri, Grazia D’Amico, Agata Grazia Federico, Concetta Saccone, Salvatore Giunta, Salvatore Cavallaro, Sebastiano D’Agata, Velia |
| description | Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. The clinical course may range from spontaneous regression towards ganglioneuroblastoma/ganglioneuroma or maturation to a very aggressive form characterized by an extensive hypoxic area. In solid tumors, extracellular microenvironment hypoxia induces the transcription of hypoxia-inducible factors (HIFs) leading to synthesis of pro-angiogenic factor, VEGF; also, it increases extracellular adenosine production from ATP breakdown. To date, the role of this nucleoside in the hypoxic/angiogenic pathway characterizing the core of cancer mass has not been investigated yet. Therefore, the aim of the present study was to analyze the adenosine effect on modulation of the HIF-1α/2α/VEGF pathway mediated through A
3
AR binding. To this end, we have used a selective A
3
AR agonist IB-MECA or antagonist VUF 5574 in an in vitro model of malignant undifferentiated and all-trans retinoic acid (RA)-differentiated SH-SY5Y cells, representing the benign form of NB. Our results have shown that specific A
3
AR stimulation induces HIF and VEGF expression through the activation of mitogen-activated protein kinase/Erk kinase signaling cascade. In conclusion, the data suggest that A
3
AR may represent a marker of NB malignancy as well as a drug target for treatment of this solid tumor.
Graphical Abstract |
| doi_str_mv | 10.1007/s12031-019-01346-4 |
| format | article |
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3
AR binding. To this end, we have used a selective A
3
AR agonist IB-MECA or antagonist VUF 5574 in an in vitro model of malignant undifferentiated and all-trans retinoic acid (RA)-differentiated SH-SY5Y cells, representing the benign form of NB. Our results have shown that specific A
3
AR stimulation induces HIF and VEGF expression through the activation of mitogen-activated protein kinase/Erk kinase signaling cascade. In conclusion, the data suggest that A
3
AR may represent a marker of NB malignancy as well as a drug target for treatment of this solid tumor.
Graphical Abstract</description><identifier>ISSN: 0895-8696</identifier><identifier>EISSN: 1559-1166</identifier><identifier>DOI: 10.1007/s12031-019-01346-4</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adenosine ; Angiogenesis ; Biomedical and Life Sciences ; Biomedicine ; Cell Biology ; Children ; Extracellular signal-regulated kinase ; Hypoxia ; Hypoxia-inducible factors ; Kinases ; Malignancy ; MAP kinase ; Modulation ; Neuroblastoma ; Neurochemistry ; Neurology ; Neuromodulation ; Neurosciences ; Protein kinase ; Proteomics ; Regression analysis ; Retinoic acid ; Solid tumors ; Transcription factors ; Tumors ; Vascular endothelial growth factor</subject><ispartof>Journal of molecular neuroscience, 2019-09, Vol.69 (1), p.166-176</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2019</rights><rights>Journal of Molecular Neuroscience is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2674-1ef3f452e28b7fc1ce62ca18b731f355a9dd556d5279098c8372c180e20f577d3</citedby><cites>FETCH-LOGICAL-c2674-1ef3f452e28b7fc1ce62ca18b731f355a9dd556d5279098c8372c180e20f577d3</cites><orcidid>0000-0003-1114-8265</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids></links><search><creatorcontrib>Maugeri, Grazia</creatorcontrib><creatorcontrib>D’Amico, Agata Grazia</creatorcontrib><creatorcontrib>Federico, Concetta</creatorcontrib><creatorcontrib>Saccone, Salvatore</creatorcontrib><creatorcontrib>Giunta, Salvatore</creatorcontrib><creatorcontrib>Cavallaro, Sebastiano</creatorcontrib><creatorcontrib>D’Agata, Velia</creatorcontrib><title>Involvement of A3 Adenosine Receptor in Neuroblastoma Progression via Modulation of the Hypoxic/Angiogenic Pathway</title><title>Journal of molecular neuroscience</title><addtitle>J Mol Neurosci</addtitle><description>Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. The clinical course may range from spontaneous regression towards ganglioneuroblastoma/ganglioneuroma or maturation to a very aggressive form characterized by an extensive hypoxic area. In solid tumors, extracellular microenvironment hypoxia induces the transcription of hypoxia-inducible factors (HIFs) leading to synthesis of pro-angiogenic factor, VEGF; also, it increases extracellular adenosine production from ATP breakdown. To date, the role of this nucleoside in the hypoxic/angiogenic pathway characterizing the core of cancer mass has not been investigated yet. Therefore, the aim of the present study was to analyze the adenosine effect on modulation of the HIF-1α/2α/VEGF pathway mediated through A
3
AR binding. To this end, we have used a selective A
3
AR agonist IB-MECA or antagonist VUF 5574 in an in vitro model of malignant undifferentiated and all-trans retinoic acid (RA)-differentiated SH-SY5Y cells, representing the benign form of NB. Our results have shown that specific A
3
AR stimulation induces HIF and VEGF expression through the activation of mitogen-activated protein kinase/Erk kinase signaling cascade. In conclusion, the data suggest that A
3
AR may represent a marker of NB malignancy as well as a drug target for treatment of this solid tumor.
Graphical Abstract</description><subject>Adenosine</subject><subject>Angiogenesis</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Biology</subject><subject>Children</subject><subject>Extracellular signal-regulated kinase</subject><subject>Hypoxia</subject><subject>Hypoxia-inducible factors</subject><subject>Kinases</subject><subject>Malignancy</subject><subject>MAP kinase</subject><subject>Modulation</subject><subject>Neuroblastoma</subject><subject>Neurochemistry</subject><subject>Neurology</subject><subject>Neuromodulation</subject><subject>Neurosciences</subject><subject>Protein kinase</subject><subject>Proteomics</subject><subject>Regression analysis</subject><subject>Retinoic acid</subject><subject>Solid tumors</subject><subject>Transcription factors</subject><subject>Tumors</subject><subject>Vascular endothelial growth factor</subject><issn>0895-8696</issn><issn>1559-1166</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kU1rGzEQhkVpIK7TP5CToJdettGMVvtxNKFNAk4TQnoWsnbWUVhLjrTr1P--ch0o9JDDMAw878vAw9g5iG8gRH2RAIWEQkCbR5ZVUX5gM1CqLQCq6iObiaZVRVO11Sn7lNKzEAglNDMWb_wuDDvakB956PlC8kVHPiTniT-Qpe0YInee_6QphtVg0hg2ht_HsI6Ukgue75zht6GbBjMezlwyPhG_3m_Db2cvFn7twpq8s_zejE-vZn_GTnozJPr8tufs14_vj5fXxfLu6uZysSwsVnVZAPWyLxUSNqu6t2CpQmsgHxJ6qZRpu06pqlNYt6JtbCNrtNAIQtGruu7knH099m5jeJkojXrjkqVhMJ7ClDRijYiiRMzol__Q5zBFn7_LlFQlgGzLTOGRsjGkFKnX2-g2Ju41CH3QoI8adNag_2rQh5A8hlKG_Zriv-p3Un8AKXGKmQ</recordid><startdate>20190901</startdate><enddate>20190901</enddate><creator>Maugeri, Grazia</creator><creator>D’Amico, Agata Grazia</creator><creator>Federico, Concetta</creator><creator>Saccone, Salvatore</creator><creator>Giunta, Salvatore</creator><creator>Cavallaro, Sebastiano</creator><creator>D’Agata, Velia</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QR</scope><scope>7T7</scope><scope>7TK</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7N</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1114-8265</orcidid></search><sort><creationdate>20190901</creationdate><title>Involvement of A3 Adenosine Receptor in Neuroblastoma Progression via Modulation of the Hypoxic/Angiogenic Pathway</title><author>Maugeri, Grazia ; D’Amico, Agata Grazia ; Federico, Concetta ; Saccone, Salvatore ; Giunta, Salvatore ; Cavallaro, Sebastiano ; D’Agata, Velia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2674-1ef3f452e28b7fc1ce62ca18b731f355a9dd556d5279098c8372c180e20f577d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adenosine</topic><topic>Angiogenesis</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell Biology</topic><topic>Children</topic><topic>Extracellular signal-regulated kinase</topic><topic>Hypoxia</topic><topic>Hypoxia-inducible factors</topic><topic>Kinases</topic><topic>Malignancy</topic><topic>MAP kinase</topic><topic>Modulation</topic><topic>Neuroblastoma</topic><topic>Neurochemistry</topic><topic>Neurology</topic><topic>Neuromodulation</topic><topic>Neurosciences</topic><topic>Protein kinase</topic><topic>Proteomics</topic><topic>Regression analysis</topic><topic>Retinoic acid</topic><topic>Solid tumors</topic><topic>Transcription factors</topic><topic>Tumors</topic><topic>Vascular endothelial growth factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Maugeri, Grazia</creatorcontrib><creatorcontrib>D’Amico, Agata Grazia</creatorcontrib><creatorcontrib>Federico, Concetta</creatorcontrib><creatorcontrib>Saccone, Salvatore</creatorcontrib><creatorcontrib>Giunta, Salvatore</creatorcontrib><creatorcontrib>Cavallaro, Sebastiano</creatorcontrib><creatorcontrib>D’Agata, Velia</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Chemoreception Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of molecular neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Maugeri, Grazia</au><au>D’Amico, Agata Grazia</au><au>Federico, Concetta</au><au>Saccone, Salvatore</au><au>Giunta, Salvatore</au><au>Cavallaro, Sebastiano</au><au>D’Agata, Velia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Involvement of A3 Adenosine Receptor in Neuroblastoma Progression via Modulation of the Hypoxic/Angiogenic Pathway</atitle><jtitle>Journal of molecular neuroscience</jtitle><stitle>J Mol Neurosci</stitle><date>2019-09-01</date><risdate>2019</risdate><volume>69</volume><issue>1</issue><spage>166</spage><epage>176</epage><pages>166-176</pages><issn>0895-8696</issn><eissn>1559-1166</eissn><abstract>Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. The clinical course may range from spontaneous regression towards ganglioneuroblastoma/ganglioneuroma or maturation to a very aggressive form characterized by an extensive hypoxic area. In solid tumors, extracellular microenvironment hypoxia induces the transcription of hypoxia-inducible factors (HIFs) leading to synthesis of pro-angiogenic factor, VEGF; also, it increases extracellular adenosine production from ATP breakdown. To date, the role of this nucleoside in the hypoxic/angiogenic pathway characterizing the core of cancer mass has not been investigated yet. Therefore, the aim of the present study was to analyze the adenosine effect on modulation of the HIF-1α/2α/VEGF pathway mediated through A
3
AR binding. To this end, we have used a selective A
3
AR agonist IB-MECA or antagonist VUF 5574 in an in vitro model of malignant undifferentiated and all-trans retinoic acid (RA)-differentiated SH-SY5Y cells, representing the benign form of NB. Our results have shown that specific A
3
AR stimulation induces HIF and VEGF expression through the activation of mitogen-activated protein kinase/Erk kinase signaling cascade. In conclusion, the data suggest that A
3
AR may represent a marker of NB malignancy as well as a drug target for treatment of this solid tumor.
Graphical Abstract</abstract><cop>New York</cop><pub>Springer US</pub><doi>10.1007/s12031-019-01346-4</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-1114-8265</orcidid></addata></record> |
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| subjects | Adenosine Angiogenesis Biomedical and Life Sciences Biomedicine Cell Biology Children Extracellular signal-regulated kinase Hypoxia Hypoxia-inducible factors Kinases Malignancy MAP kinase Modulation Neuroblastoma Neurochemistry Neurology Neuromodulation Neurosciences Protein kinase Proteomics Regression analysis Retinoic acid Solid tumors Transcription factors Tumors Vascular endothelial growth factor |
| title | Involvement of A3 Adenosine Receptor in Neuroblastoma Progression via Modulation of the Hypoxic/Angiogenic Pathway |
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