Autoantibodies Specific to ERα are Involved in Tamoxifen Resistance in Hormone Receptor Positive Breast Cancer
Tamoxifen resistance is a major hurdle in the treatment of estrogen receptor (ER)-positive breast cancer. The mechanisms of tamoxifen resistance are not fully understood although several underlying molecular events have been suggested. Recently, we identified autoantibodies reacting with membrane-as...
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MDPI AG
2019-07-01
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| Online Access: | https://www.mdpi.com/2073-4409/8/7/750 |
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| author | Angela Maselli Stefania Parlato Rossella Puglisi Carla Raggi Massimo Spada Daniele Macchia Giada Pontecorvi Elisabetta Iessi Maria Teresa Pagano Francesca Cirulli Lucia Gabriele Alessandra Carè Patrizia Vici Laura Pizzuti Maddalena Barba Paola Matarrese Marina Pierdominici Elena Ortona |
| author_facet | Angela Maselli Stefania Parlato Rossella Puglisi Carla Raggi Massimo Spada Daniele Macchia Giada Pontecorvi Elisabetta Iessi Maria Teresa Pagano Francesca Cirulli Lucia Gabriele Alessandra Carè Patrizia Vici Laura Pizzuti Maddalena Barba Paola Matarrese Marina Pierdominici Elena Ortona |
| author_sort | Angela Maselli |
| collection | DOAJ |
| description | Tamoxifen resistance is a major hurdle in the treatment of estrogen receptor (ER)-positive breast cancer. The mechanisms of tamoxifen resistance are not fully understood although several underlying molecular events have been suggested. Recently, we identified autoantibodies reacting with membrane-associated ERα (anti-ERα Abs) in sera of breast cancer patients, able to promote tumor growth. Here, we investigated whether anti-ERα Abs purified from sera of ER-positive breast cancer patients could contribute to tamoxifen resistance. Anti-ERα Abs inhibited tamoxifen-mediated effects on cell cycle and proliferation in MCF-7 cells. Moreover, anti-ERα Abs hampered the tamoxifen-mediated reduction of tumor growth in SCID mice xenografted with breast tumor. Notably, simvastatin-mediated disaggregation of lipid rafts, where membrane-associated ERα is embedded, restored tamoxifen sensitivity, preventing anti-ERα Abs effects. In conclusion, detection of serum anti-ERα Abs may help predict tamoxifen resistance and concur to appropriately inform therapeutic decisions concerning hormone therapy in ER-positive breast cancer patients. |
| first_indexed | 2024-03-12T10:46:09Z |
| format | Article |
| id | doaj.art-02c227cb9c2b4127a08c583d779635ac |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T10:46:09Z |
| publishDate | 2019-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-02c227cb9c2b4127a08c583d779635ac2023-09-02T07:24:42ZengMDPI AGCells2073-44092019-07-018775010.3390/cells8070750cells8070750Autoantibodies Specific to ERα are Involved in Tamoxifen Resistance in Hormone Receptor Positive Breast CancerAngela Maselli0Stefania Parlato1Rossella Puglisi2Carla Raggi3Massimo Spada4Daniele Macchia5Giada Pontecorvi6Elisabetta Iessi7Maria Teresa Pagano8Francesca Cirulli9Lucia Gabriele10Alessandra Carè11Patrizia Vici12Laura Pizzuti13Maddalena Barba14Paola Matarrese15Marina Pierdominici16Elena Ortona17Center for Gender Specific Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyCenter for Gender Specific Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyNational Centre for the Control and the Evaluation of Medicines, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyCenter for Gender Specific Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyCenter for Gender Specific Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyCenter for Gender Specific Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyCenter for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyCenter for Gender Specific Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyDivision of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, 00128 Rome, ItalyDivision of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, 00128 Rome, ItalyDivision of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, 00128 Rome, ItalyCenter for Gender Specific Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyCenter for Gender Specific Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyCenter for Gender Specific Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyTamoxifen resistance is a major hurdle in the treatment of estrogen receptor (ER)-positive breast cancer. The mechanisms of tamoxifen resistance are not fully understood although several underlying molecular events have been suggested. Recently, we identified autoantibodies reacting with membrane-associated ERα (anti-ERα Abs) in sera of breast cancer patients, able to promote tumor growth. Here, we investigated whether anti-ERα Abs purified from sera of ER-positive breast cancer patients could contribute to tamoxifen resistance. Anti-ERα Abs inhibited tamoxifen-mediated effects on cell cycle and proliferation in MCF-7 cells. Moreover, anti-ERα Abs hampered the tamoxifen-mediated reduction of tumor growth in SCID mice xenografted with breast tumor. Notably, simvastatin-mediated disaggregation of lipid rafts, where membrane-associated ERα is embedded, restored tamoxifen sensitivity, preventing anti-ERα Abs effects. In conclusion, detection of serum anti-ERα Abs may help predict tamoxifen resistance and concur to appropriately inform therapeutic decisions concerning hormone therapy in ER-positive breast cancer patients.https://www.mdpi.com/2073-4409/8/7/750autoantibodiesestrogen receptorbreast cancertamoxifenlipid raftsstatins |
| spellingShingle | Angela Maselli Stefania Parlato Rossella Puglisi Carla Raggi Massimo Spada Daniele Macchia Giada Pontecorvi Elisabetta Iessi Maria Teresa Pagano Francesca Cirulli Lucia Gabriele Alessandra Carè Patrizia Vici Laura Pizzuti Maddalena Barba Paola Matarrese Marina Pierdominici Elena Ortona Autoantibodies Specific to ERα are Involved in Tamoxifen Resistance in Hormone Receptor Positive Breast Cancer Cells autoantibodies estrogen receptor breast cancer tamoxifen lipid rafts statins |
| title | Autoantibodies Specific to ERα are Involved in Tamoxifen Resistance in Hormone Receptor Positive Breast Cancer |
| title_full | Autoantibodies Specific to ERα are Involved in Tamoxifen Resistance in Hormone Receptor Positive Breast Cancer |
| title_fullStr | Autoantibodies Specific to ERα are Involved in Tamoxifen Resistance in Hormone Receptor Positive Breast Cancer |
| title_full_unstemmed | Autoantibodies Specific to ERα are Involved in Tamoxifen Resistance in Hormone Receptor Positive Breast Cancer |
| title_short | Autoantibodies Specific to ERα are Involved in Tamoxifen Resistance in Hormone Receptor Positive Breast Cancer |
| title_sort | autoantibodies specific to erα are involved in tamoxifen resistance in hormone receptor positive breast cancer |
| topic | autoantibodies estrogen receptor breast cancer tamoxifen lipid rafts statins |
| url | https://www.mdpi.com/2073-4409/8/7/750 |
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