BCG-induced cytokine release in bladder cancer cells is regulated by Ca 2+ signaling
Bacillus Calmette-Guérin (BCG) is widely used in the clinic to effectively treat superficial urinary bladder cancer. However, a significant proportion of patients who fail to respond to BCG risk cystectomy or death. Though more than 3 million cancer treatments with BCG occur annually, surprisingly l...
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| Veröffentlicht in: | Molecular oncology 2019-02, Vol.13 (2), p.202-211 |
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| creator | Ibarra, Cristián Karlsson, Marie Codeluppi, Simone Varas-Godoy, Manuel Zhang, Songbai Louhivuori, Lauri Mangsbo, Sara Hosseini, Arad Soltani, Navid Kaba, Rahim Kalle Lundgren, T Hosseini, Abolfazl Tanaka, Nobuyuki Oya, Mototsugu Wiklund, Peter Miyakawa, Ayako Uhlén, Per |
| description | Bacillus Calmette-Guérin (BCG) is widely used in the clinic to effectively treat superficial urinary bladder cancer. However, a significant proportion of patients who fail to respond to BCG risk cystectomy or death. Though more than 3 million cancer treatments with BCG occur annually, surprisingly little is known about the initial signaling cascades activated by BCG. Here, we report that BCG induces a rapid intracellular Ca
(calcium ion) signal in bladder cancer cells that is essential for activating the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and for synthesizing and secreting proinflammatory cytokines, including interleukin 8 (IL-8). A similar Ca
response was observed when cells were exposed to the supernatant of BCG. Studying cellular molecular mechanisms involved in the BCG signaling event, we found pivotal roles for phospholipase C and the Toll-like receptor 4. Further assessment revealed that this signaling pathway induces synthesis of IL-8, whereas exocytosis appeared to be controlled by global Ca
signaling. These results shed new light on the molecular mechanisms underlying BCG treatment of bladder cancer, which can help in improving therapeutic efficacy and reducing adverse side effects. |
| doi_str_mv | 10.1002/1878-0261.12397 |
| format | Article |
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(calcium ion) signal in bladder cancer cells that is essential for activating the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and for synthesizing and secreting proinflammatory cytokines, including interleukin 8 (IL-8). A similar Ca
response was observed when cells were exposed to the supernatant of BCG. Studying cellular molecular mechanisms involved in the BCG signaling event, we found pivotal roles for phospholipase C and the Toll-like receptor 4. Further assessment revealed that this signaling pathway induces synthesis of IL-8, whereas exocytosis appeared to be controlled by global Ca
signaling. These results shed new light on the molecular mechanisms underlying BCG treatment of bladder cancer, which can help in improving therapeutic efficacy and reducing adverse side effects.</description><identifier>ISSN: 1574-7891</identifier><identifier>EISSN: 1878-0261</identifier><identifier>DOI: 10.1002/1878-0261.12397</identifier><identifier>PMID: 30358081</identifier><language>eng</language><publisher>United States: John Wiley & Sons, Inc</publisher><subject>Bacillus Calmette-Guerin vaccine ; BCG ; Bladder cancer ; Calcium (intracellular) ; Calcium - metabolism ; Calcium Signaling ; Calcium signalling ; Cancer ; Cell culture ; Cell Line, Tumor ; Cytokines ; Cytokines - metabolism ; Cytosol - metabolism ; Design ; Endoplasmic reticulum ; Exocytosis ; Experiments ; Humans ; Inflammation ; Interleukin 8 ; Interleukin-8 - metabolism ; Kinases ; Lymphocytes B ; Molecular modelling ; Mycobacterium bovis - metabolism ; NF-kappa B - metabolism ; Phospholipase C ; Proteins ; Signal transduction ; Toll-Like Receptor 4 - metabolism ; Toll-like receptors ; Tumors ; Urinary bladder ; Urinary Bladder Neoplasms - metabolism</subject><ispartof>Molecular oncology, 2019-02, Vol.13 (2), p.202-211</ispartof><rights>2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.</rights><rights>2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1758-d619681df04b28b1fc33c992568bc384fa467698323f429503153d36a399bd993</citedby><cites>FETCH-LOGICAL-c1758-d619681df04b28b1fc33c992568bc384fa467698323f429503153d36a399bd993</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,550,776,780,860,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30358081$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:140199805$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Ibarra, Cristián</creatorcontrib><creatorcontrib>Karlsson, Marie</creatorcontrib><creatorcontrib>Codeluppi, Simone</creatorcontrib><creatorcontrib>Varas-Godoy, Manuel</creatorcontrib><creatorcontrib>Zhang, Songbai</creatorcontrib><creatorcontrib>Louhivuori, Lauri</creatorcontrib><creatorcontrib>Mangsbo, Sara</creatorcontrib><creatorcontrib>Hosseini, Arad</creatorcontrib><creatorcontrib>Soltani, Navid</creatorcontrib><creatorcontrib>Kaba, Rahim</creatorcontrib><creatorcontrib>Kalle Lundgren, T</creatorcontrib><creatorcontrib>Hosseini, Abolfazl</creatorcontrib><creatorcontrib>Tanaka, Nobuyuki</creatorcontrib><creatorcontrib>Oya, Mototsugu</creatorcontrib><creatorcontrib>Wiklund, Peter</creatorcontrib><creatorcontrib>Miyakawa, Ayako</creatorcontrib><creatorcontrib>Uhlén, Per</creatorcontrib><title>BCG-induced cytokine release in bladder cancer cells is regulated by Ca 2+ signaling</title><title>Molecular oncology</title><addtitle>Mol Oncol</addtitle><description>Bacillus Calmette-Guérin (BCG) is widely used in the clinic to effectively treat superficial urinary bladder cancer. However, a significant proportion of patients who fail to respond to BCG risk cystectomy or death. Though more than 3 million cancer treatments with BCG occur annually, surprisingly little is known about the initial signaling cascades activated by BCG. Here, we report that BCG induces a rapid intracellular Ca
(calcium ion) signal in bladder cancer cells that is essential for activating the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and for synthesizing and secreting proinflammatory cytokines, including interleukin 8 (IL-8). A similar Ca
response was observed when cells were exposed to the supernatant of BCG. Studying cellular molecular mechanisms involved in the BCG signaling event, we found pivotal roles for phospholipase C and the Toll-like receptor 4. Further assessment revealed that this signaling pathway induces synthesis of IL-8, whereas exocytosis appeared to be controlled by global Ca
signaling. These results shed new light on the molecular mechanisms underlying BCG treatment of bladder cancer, which can help in improving therapeutic efficacy and reducing adverse side effects.</description><subject>Bacillus Calmette-Guerin vaccine</subject><subject>BCG</subject><subject>Bladder cancer</subject><subject>Calcium (intracellular)</subject><subject>Calcium - metabolism</subject><subject>Calcium Signaling</subject><subject>Calcium signalling</subject><subject>Cancer</subject><subject>Cell culture</subject><subject>Cell Line, Tumor</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Cytosol - metabolism</subject><subject>Design</subject><subject>Endoplasmic reticulum</subject><subject>Exocytosis</subject><subject>Experiments</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Interleukin 8</subject><subject>Interleukin-8 - metabolism</subject><subject>Kinases</subject><subject>Lymphocytes B</subject><subject>Molecular modelling</subject><subject>Mycobacterium bovis - metabolism</subject><subject>NF-kappa B - metabolism</subject><subject>Phospholipase C</subject><subject>Proteins</subject><subject>Signal transduction</subject><subject>Toll-Like Receptor 4 - metabolism</subject><subject>Toll-like receptors</subject><subject>Tumors</subject><subject>Urinary bladder</subject><subject>Urinary Bladder Neoplasms - metabolism</subject><issn>1574-7891</issn><issn>1878-0261</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>D8T</sourceid><recordid>eNo9kEtLAzEURoMotlbX7iTgUqbNY5JJljpoFQpu6jrkNSXtdKYmHaT_3hlbu7qXy_k-LgeAe4ymGCEyw6IQGSIcTzGhsrgA4_Plst9ZkWeFkHgEblJaI8S45PIajCiiTCCBx2D5Us6z0LjOegftYd9uQuNh9LXXycPQQFNr53yEVjd2GL6uEwypR1Zdrfd9yhxgqSF5gimsGl2HZnULripdJ393mhPw9fa6LN-zxef8o3xeZBYXTGSOY8kFdhXKDREGV5ZSKyVhXBhLRV7pnBdcCkpolRPJEMWMOso1ldI4KekEZMfe9ON3nVG7GLY6HlSrgzqdNv3mVS5yjkTPPx75XWy_O5_2at12sf85KUIkIqzgbKBmR8rGNqXoq3MvRmqwrgbHanCs_qz3iYdTb2e23p35f830Fy2QefE</recordid><startdate>201902</startdate><enddate>201902</enddate><creator>Ibarra, Cristián</creator><creator>Karlsson, Marie</creator><creator>Codeluppi, Simone</creator><creator>Varas-Godoy, Manuel</creator><creator>Zhang, Songbai</creator><creator>Louhivuori, Lauri</creator><creator>Mangsbo, Sara</creator><creator>Hosseini, Arad</creator><creator>Soltani, Navid</creator><creator>Kaba, Rahim</creator><creator>Kalle Lundgren, T</creator><creator>Hosseini, Abolfazl</creator><creator>Tanaka, Nobuyuki</creator><creator>Oya, Mototsugu</creator><creator>Wiklund, Peter</creator><creator>Miyakawa, Ayako</creator><creator>Uhlén, Per</creator><general>John Wiley & Sons, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>201902</creationdate><title>BCG-induced cytokine release in bladder cancer cells is regulated by Ca 2+ signaling</title><author>Ibarra, Cristián ; Karlsson, Marie ; Codeluppi, Simone ; Varas-Godoy, Manuel ; Zhang, Songbai ; Louhivuori, Lauri ; Mangsbo, Sara ; Hosseini, Arad ; Soltani, Navid ; Kaba, Rahim ; Kalle Lundgren, T ; Hosseini, Abolfazl ; Tanaka, Nobuyuki ; Oya, Mototsugu ; Wiklund, Peter ; Miyakawa, Ayako ; Uhlén, Per</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1758-d619681df04b28b1fc33c992568bc384fa467698323f429503153d36a399bd993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Bacillus Calmette-Guerin vaccine</topic><topic>BCG</topic><topic>Bladder cancer</topic><topic>Calcium (intracellular)</topic><topic>Calcium - metabolism</topic><topic>Calcium Signaling</topic><topic>Calcium signalling</topic><topic>Cancer</topic><topic>Cell culture</topic><topic>Cell Line, Tumor</topic><topic>Cytokines</topic><topic>Cytokines - metabolism</topic><topic>Cytosol - metabolism</topic><topic>Design</topic><topic>Endoplasmic reticulum</topic><topic>Exocytosis</topic><topic>Experiments</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Interleukin 8</topic><topic>Interleukin-8 - metabolism</topic><topic>Kinases</topic><topic>Lymphocytes B</topic><topic>Molecular modelling</topic><topic>Mycobacterium bovis - metabolism</topic><topic>NF-kappa B - metabolism</topic><topic>Phospholipase C</topic><topic>Proteins</topic><topic>Signal transduction</topic><topic>Toll-Like Receptor 4 - metabolism</topic><topic>Toll-like receptors</topic><topic>Tumors</topic><topic>Urinary bladder</topic><topic>Urinary Bladder Neoplasms - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ibarra, Cristián</creatorcontrib><creatorcontrib>Karlsson, Marie</creatorcontrib><creatorcontrib>Codeluppi, Simone</creatorcontrib><creatorcontrib>Varas-Godoy, Manuel</creatorcontrib><creatorcontrib>Zhang, Songbai</creatorcontrib><creatorcontrib>Louhivuori, Lauri</creatorcontrib><creatorcontrib>Mangsbo, Sara</creatorcontrib><creatorcontrib>Hosseini, Arad</creatorcontrib><creatorcontrib>Soltani, Navid</creatorcontrib><creatorcontrib>Kaba, Rahim</creatorcontrib><creatorcontrib>Kalle Lundgren, T</creatorcontrib><creatorcontrib>Hosseini, Abolfazl</creatorcontrib><creatorcontrib>Tanaka, Nobuyuki</creatorcontrib><creatorcontrib>Oya, Mototsugu</creatorcontrib><creatorcontrib>Wiklund, Peter</creatorcontrib><creatorcontrib>Miyakawa, Ayako</creatorcontrib><creatorcontrib>Uhlén, Per</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</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>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Molecular oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ibarra, Cristián</au><au>Karlsson, Marie</au><au>Codeluppi, Simone</au><au>Varas-Godoy, Manuel</au><au>Zhang, Songbai</au><au>Louhivuori, Lauri</au><au>Mangsbo, Sara</au><au>Hosseini, Arad</au><au>Soltani, Navid</au><au>Kaba, Rahim</au><au>Kalle Lundgren, T</au><au>Hosseini, Abolfazl</au><au>Tanaka, Nobuyuki</au><au>Oya, Mototsugu</au><au>Wiklund, Peter</au><au>Miyakawa, Ayako</au><au>Uhlén, Per</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>BCG-induced cytokine release in bladder cancer cells is regulated by Ca 2+ signaling</atitle><jtitle>Molecular oncology</jtitle><addtitle>Mol Oncol</addtitle><date>2019-02</date><risdate>2019</risdate><volume>13</volume><issue>2</issue><spage>202</spage><epage>211</epage><pages>202-211</pages><issn>1574-7891</issn><eissn>1878-0261</eissn><abstract>Bacillus Calmette-Guérin (BCG) is widely used in the clinic to effectively treat superficial urinary bladder cancer. However, a significant proportion of patients who fail to respond to BCG risk cystectomy or death. Though more than 3 million cancer treatments with BCG occur annually, surprisingly little is known about the initial signaling cascades activated by BCG. Here, we report that BCG induces a rapid intracellular Ca
(calcium ion) signal in bladder cancer cells that is essential for activating the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and for synthesizing and secreting proinflammatory cytokines, including interleukin 8 (IL-8). A similar Ca
response was observed when cells were exposed to the supernatant of BCG. Studying cellular molecular mechanisms involved in the BCG signaling event, we found pivotal roles for phospholipase C and the Toll-like receptor 4. Further assessment revealed that this signaling pathway induces synthesis of IL-8, whereas exocytosis appeared to be controlled by global Ca
signaling. These results shed new light on the molecular mechanisms underlying BCG treatment of bladder cancer, which can help in improving therapeutic efficacy and reducing adverse side effects.</abstract><cop>United States</cop><pub>John Wiley & Sons, Inc</pub><pmid>30358081</pmid><doi>10.1002/1878-0261.12397</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SWEPUB Freely available online; Wiley Online Library Open Access; PubMed Central |
| subjects | Bacillus Calmette-Guerin vaccine BCG Bladder cancer Calcium (intracellular) Calcium - metabolism Calcium Signaling Calcium signalling Cancer Cell culture Cell Line, Tumor Cytokines Cytokines - metabolism Cytosol - metabolism Design Endoplasmic reticulum Exocytosis Experiments Humans Inflammation Interleukin 8 Interleukin-8 - metabolism Kinases Lymphocytes B Molecular modelling Mycobacterium bovis - metabolism NF-kappa B - metabolism Phospholipase C Proteins Signal transduction Toll-Like Receptor 4 - metabolism Toll-like receptors Tumors Urinary bladder Urinary Bladder Neoplasms - metabolism |
| title | BCG-induced cytokine release in bladder cancer cells is regulated by Ca 2+ signaling |
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