The Calcium-Sensing Receptor is A Marker and Potential Driver of Neuroendocrine Differentiation in Prostate Cancer
The mechanisms underlying neuroendocrine (NE) differentiation in prostate cancer (PCa) remain mostly uncharacterized. Since a deregulated calcium homeostasis has been reported in neuroendocrine prostate cancer (NEPC), we explored herein the link between NE differentiation and the calcium-sensing rec...
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| Veröffentlicht in: | Cancers 2020-04, Vol.12 (4), p.860 |
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| creator | Bery, Fanny Cancel, Mathilde Chantôme, Aurélie Guibon, Roseline Bruyère, Franck Rozet, François Mahéo, Karine Fromont, Gaëlle |
| description | The mechanisms underlying neuroendocrine (NE) differentiation in prostate cancer (PCa) remain mostly uncharacterized. Since a deregulated calcium homeostasis has been reported in neuroendocrine prostate cancer (NEPC), we explored herein the link between NE differentiation and the calcium-sensing receptor (CaSR). CaSR expression was evaluated by immunohistochemistry-together with NE markers-on tissue microarrays containing samples of normal prostate, localized PCa, metastatic castration resistant PCa (MCRPC) and NEPC. In prostate tissues, we observed a strong association between CaSR and chromogranin expression. Both markers were strongly expressed in all cases of NEPC and co-expression was confirmed by double immunostaining. In MCRPC, the expression of CaSR was significantly associated with shorter overall survival. The involvement of CaSR in NE differentiation was evaluated in PCa cell lines. Inhibition of CaSR led to decrease the expression of neuronal (NSE, βtubulinIII) and NE (chromogranin, synaptophysin) markers in the NE PCa cell line NCI-H660. A decrease of neuronal and NE markers was also observed in siCaSR-transfected PC3 and 22RV1 cells, respectively, whereas CaSR activation increased both NSE and synaptophysin expression in PC3 cells. These results strongly suggest that CaSR is a marker and a driver of NE differentiation in PCa and emphasize the potential of CaSR directed therapy for NEPC patients. |
| doi_str_mv | 10.3390/cancers12040860 |
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Since a deregulated calcium homeostasis has been reported in neuroendocrine prostate cancer (NEPC), we explored herein the link between NE differentiation and the calcium-sensing receptor (CaSR). CaSR expression was evaluated by immunohistochemistry-together with NE markers-on tissue microarrays containing samples of normal prostate, localized PCa, metastatic castration resistant PCa (MCRPC) and NEPC. In prostate tissues, we observed a strong association between CaSR and chromogranin expression. Both markers were strongly expressed in all cases of NEPC and co-expression was confirmed by double immunostaining. In MCRPC, the expression of CaSR was significantly associated with shorter overall survival. The involvement of CaSR in NE differentiation was evaluated in PCa cell lines. Inhibition of CaSR led to decrease the expression of neuronal (NSE, βtubulinIII) and NE (chromogranin, synaptophysin) markers in the NE PCa cell line NCI-H660. A decrease of neuronal and NE markers was also observed in siCaSR-transfected PC3 and 22RV1 cells, respectively, whereas CaSR activation increased both NSE and synaptophysin expression in PC3 cells. These results strongly suggest that CaSR is a marker and a driver of NE differentiation in PCa and emphasize the potential of CaSR directed therapy for NEPC patients.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers12040860</identifier><identifier>PMID: 32252342</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Androgens ; Calcium homeostasis ; Calcium-sensing receptors ; Castration ; Cell activation ; Cell differentiation ; Homeostasis ; Immunohistochemistry ; Medical prognosis ; Metastases ; Prostate cancer ; Proteins ; Synaptophysin ; Vitamin D ; Vitamin deficiency</subject><ispartof>Cancers, 2020-04, Vol.12 (4), p.860</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c487t-ffb29044df90615231555e86a967ce5d1fc7a6517ae4e1972b8cf1712d8662403</citedby><cites>FETCH-LOGICAL-c487t-ffb29044df90615231555e86a967ce5d1fc7a6517ae4e1972b8cf1712d8662403</cites><orcidid>0000-0003-1162-214X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226072/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226072/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32252342$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bery, Fanny</creatorcontrib><creatorcontrib>Cancel, Mathilde</creatorcontrib><creatorcontrib>Chantôme, Aurélie</creatorcontrib><creatorcontrib>Guibon, Roseline</creatorcontrib><creatorcontrib>Bruyère, Franck</creatorcontrib><creatorcontrib>Rozet, François</creatorcontrib><creatorcontrib>Mahéo, Karine</creatorcontrib><creatorcontrib>Fromont, Gaëlle</creatorcontrib><title>The Calcium-Sensing Receptor is A Marker and Potential Driver of Neuroendocrine Differentiation in Prostate Cancer</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>The mechanisms underlying neuroendocrine (NE) differentiation in prostate cancer (PCa) remain mostly uncharacterized. Since a deregulated calcium homeostasis has been reported in neuroendocrine prostate cancer (NEPC), we explored herein the link between NE differentiation and the calcium-sensing receptor (CaSR). CaSR expression was evaluated by immunohistochemistry-together with NE markers-on tissue microarrays containing samples of normal prostate, localized PCa, metastatic castration resistant PCa (MCRPC) and NEPC. In prostate tissues, we observed a strong association between CaSR and chromogranin expression. Both markers were strongly expressed in all cases of NEPC and co-expression was confirmed by double immunostaining. In MCRPC, the expression of CaSR was significantly associated with shorter overall survival. The involvement of CaSR in NE differentiation was evaluated in PCa cell lines. Inhibition of CaSR led to decrease the expression of neuronal (NSE, βtubulinIII) and NE (chromogranin, synaptophysin) markers in the NE PCa cell line NCI-H660. A decrease of neuronal and NE markers was also observed in siCaSR-transfected PC3 and 22RV1 cells, respectively, whereas CaSR activation increased both NSE and synaptophysin expression in PC3 cells. These results strongly suggest that CaSR is a marker and a driver of NE differentiation in PCa and emphasize the potential of CaSR directed therapy for NEPC patients.</description><subject>Androgens</subject><subject>Calcium homeostasis</subject><subject>Calcium-sensing receptors</subject><subject>Castration</subject><subject>Cell activation</subject><subject>Cell differentiation</subject><subject>Homeostasis</subject><subject>Immunohistochemistry</subject><subject>Medical prognosis</subject><subject>Metastases</subject><subject>Prostate cancer</subject><subject>Proteins</subject><subject>Synaptophysin</subject><subject>Vitamin D</subject><subject>Vitamin deficiency</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkUlPBCEQhYnRqFHP3gyJFy-tLN3QfTEx45q4xeVMGLpQtAdG6Dbx38uMS0a5QODj1at6CG1Tss95Qw6M9gZiooyUpBZkCa0zIlkhRFMuL5zX0FZKLyQvzqkUchWtccYqxku2juLDM-CR7owbJsU9-OT8E74DA9M-ROwSPsJXOr5CxNq3-Db04HunO3wc3Xu-DBZfwxAD-DaY6DzgY2ctxDnVu-Cx8_g2htTrflZnZngTrVjdJdj63jfQ4-nJw-i8uLw5uxgdXRamrGVfWDtmDSnL1jZE0GyXVlUFtdCNkAaqllojtaio1FACbSQb18ZSSVlbC8FKwjfQ4ZfudBhPoDXZU9SdmkY30fFDBe3U3xfvntVTeFeSMZGHlwX2vgVieBsg9WrikoGu0x7CkBTjtWSC5poZ3f2HvoQh-tzenCKiZqLO1MEXZfJEUgT7a4YSNYtU_Ys0_9hZ7OGX_wmQfwI36p5H</recordid><startdate>20200402</startdate><enddate>20200402</enddate><creator>Bery, Fanny</creator><creator>Cancel, Mathilde</creator><creator>Chantôme, Aurélie</creator><creator>Guibon, Roseline</creator><creator>Bruyère, Franck</creator><creator>Rozet, François</creator><creator>Mahéo, Karine</creator><creator>Fromont, Gaëlle</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</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>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1162-214X</orcidid></search><sort><creationdate>20200402</creationdate><title>The Calcium-Sensing Receptor is A Marker and Potential Driver of Neuroendocrine Differentiation in Prostate Cancer</title><author>Bery, Fanny ; Cancel, Mathilde ; Chantôme, Aurélie ; Guibon, Roseline ; Bruyère, Franck ; Rozet, François ; Mahéo, Karine ; Fromont, Gaëlle</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c487t-ffb29044df90615231555e86a967ce5d1fc7a6517ae4e1972b8cf1712d8662403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Androgens</topic><topic>Calcium homeostasis</topic><topic>Calcium-sensing receptors</topic><topic>Castration</topic><topic>Cell activation</topic><topic>Cell differentiation</topic><topic>Homeostasis</topic><topic>Immunohistochemistry</topic><topic>Medical prognosis</topic><topic>Metastases</topic><topic>Prostate cancer</topic><topic>Proteins</topic><topic>Synaptophysin</topic><topic>Vitamin D</topic><topic>Vitamin deficiency</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bery, Fanny</creatorcontrib><creatorcontrib>Cancel, Mathilde</creatorcontrib><creatorcontrib>Chantôme, Aurélie</creatorcontrib><creatorcontrib>Guibon, Roseline</creatorcontrib><creatorcontrib>Bruyère, Franck</creatorcontrib><creatorcontrib>Rozet, François</creatorcontrib><creatorcontrib>Mahéo, Karine</creatorcontrib><creatorcontrib>Fromont, Gaëlle</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</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>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Access via ProQuest (Open Access)</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 Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bery, Fanny</au><au>Cancel, Mathilde</au><au>Chantôme, Aurélie</au><au>Guibon, Roseline</au><au>Bruyère, Franck</au><au>Rozet, François</au><au>Mahéo, Karine</au><au>Fromont, Gaëlle</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Calcium-Sensing Receptor is A Marker and Potential Driver of Neuroendocrine Differentiation in Prostate Cancer</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2020-04-02</date><risdate>2020</risdate><volume>12</volume><issue>4</issue><spage>860</spage><pages>860-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>The mechanisms underlying neuroendocrine (NE) differentiation in prostate cancer (PCa) remain mostly uncharacterized. 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A decrease of neuronal and NE markers was also observed in siCaSR-transfected PC3 and 22RV1 cells, respectively, whereas CaSR activation increased both NSE and synaptophysin expression in PC3 cells. These results strongly suggest that CaSR is a marker and a driver of NE differentiation in PCa and emphasize the potential of CaSR directed therapy for NEPC patients.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>32252342</pmid><doi>10.3390/cancers12040860</doi><orcidid>https://orcid.org/0000-0003-1162-214X</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; PubMed Central |
| subjects | Androgens Calcium homeostasis Calcium-sensing receptors Castration Cell activation Cell differentiation Homeostasis Immunohistochemistry Medical prognosis Metastases Prostate cancer Proteins Synaptophysin Vitamin D Vitamin deficiency |
| title | The Calcium-Sensing Receptor is A Marker and Potential Driver of Neuroendocrine Differentiation in Prostate Cancer |
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