New blocking antibodies impede adhesion, migration and survival of ovarian cancer cells, highlighting MFGE8 as a potential therapeutic target of human ovarian carcinoma.
Milk Fat Globule--EGF--factor VIII (MFGE8), also called lactadherin, is a secreted protein, which binds extracellularly to phosphatidylserine and to αvβ3 and αvβ5 integrins. On human and mouse cells expressing these integrins, such as endothelial cells, phagocytes and some tumors, MFGE8/lactadherin...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3745384?pdf=render |
| _version_ | 1828790070543384576 |
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| author | Lorenzo Tibaldi Shirley Leyman André Nicolas Sofie Notebaert Melissa Dewulf Thu Hoa Ngo Claudia Zuany-Amorim Nathalie Amzallag Isabelle Bernard-Pierrot Xavier Sastre-Garau Clotilde Théry |
| author_facet | Lorenzo Tibaldi Shirley Leyman André Nicolas Sofie Notebaert Melissa Dewulf Thu Hoa Ngo Claudia Zuany-Amorim Nathalie Amzallag Isabelle Bernard-Pierrot Xavier Sastre-Garau Clotilde Théry |
| author_sort | Lorenzo Tibaldi |
| collection | DOAJ |
| description | Milk Fat Globule--EGF--factor VIII (MFGE8), also called lactadherin, is a secreted protein, which binds extracellularly to phosphatidylserine and to αvβ3 and αvβ5 integrins. On human and mouse cells expressing these integrins, such as endothelial cells, phagocytes and some tumors, MFGE8/lactadherin has been shown to promote survival, epithelial to mesenchymal transition and phagocytosis. A protumoral function of MFGE8 has consequently been documented for a few types of human cancers, including melanoma, a subtype of breast cancers, and bladder carcinoma. Inhibiting the functions of MFGE8 could thus represent a new type of therapy for human cancers. Here, we show by immunohistochemistry on a collection of human ovarian cancers that MFGE8 is overexpressed in 45% of these tumors, and we confirm that it is specifically overexpressed in the triple-negative subtype of human breast cancers. We have established new in vitro assays to measure the effect of MFGE8 on survival, adhesion and migration of human ovarian and triple-negative breast cancer cell lines. Using these assays, we could identify new MFGE8-specific monoclonal antibodies, which efficiently blocked these three tumor-promoting effects of MFGE8. Our results suggest future use of MFGE8-blocking antibodies as new anti-cancer therapeutics in subgroups of ovarian carcinoma, and triple-negative breast carcinoma patients. |
| first_indexed | 2024-12-12T01:22:50Z |
| format | Article |
| id | doaj.art-6cb2a11006d24a5a9efd1ec4b276c1ba |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T01:22:50Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6cb2a11006d24a5a9efd1ec4b276c1ba2022-12-22T00:43:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7270810.1371/journal.pone.0072708New blocking antibodies impede adhesion, migration and survival of ovarian cancer cells, highlighting MFGE8 as a potential therapeutic target of human ovarian carcinoma.Lorenzo TibaldiShirley LeymanAndré NicolasSofie NotebaertMelissa DewulfThu Hoa NgoClaudia Zuany-AmorimNathalie AmzallagIsabelle Bernard-PierrotXavier Sastre-GarauClotilde ThéryMilk Fat Globule--EGF--factor VIII (MFGE8), also called lactadherin, is a secreted protein, which binds extracellularly to phosphatidylserine and to αvβ3 and αvβ5 integrins. On human and mouse cells expressing these integrins, such as endothelial cells, phagocytes and some tumors, MFGE8/lactadherin has been shown to promote survival, epithelial to mesenchymal transition and phagocytosis. A protumoral function of MFGE8 has consequently been documented for a few types of human cancers, including melanoma, a subtype of breast cancers, and bladder carcinoma. Inhibiting the functions of MFGE8 could thus represent a new type of therapy for human cancers. Here, we show by immunohistochemistry on a collection of human ovarian cancers that MFGE8 is overexpressed in 45% of these tumors, and we confirm that it is specifically overexpressed in the triple-negative subtype of human breast cancers. We have established new in vitro assays to measure the effect of MFGE8 on survival, adhesion and migration of human ovarian and triple-negative breast cancer cell lines. Using these assays, we could identify new MFGE8-specific monoclonal antibodies, which efficiently blocked these three tumor-promoting effects of MFGE8. Our results suggest future use of MFGE8-blocking antibodies as new anti-cancer therapeutics in subgroups of ovarian carcinoma, and triple-negative breast carcinoma patients.http://europepmc.org/articles/PMC3745384?pdf=render |
| spellingShingle | Lorenzo Tibaldi Shirley Leyman André Nicolas Sofie Notebaert Melissa Dewulf Thu Hoa Ngo Claudia Zuany-Amorim Nathalie Amzallag Isabelle Bernard-Pierrot Xavier Sastre-Garau Clotilde Théry New blocking antibodies impede adhesion, migration and survival of ovarian cancer cells, highlighting MFGE8 as a potential therapeutic target of human ovarian carcinoma. PLoS ONE |
| title | New blocking antibodies impede adhesion, migration and survival of ovarian cancer cells, highlighting MFGE8 as a potential therapeutic target of human ovarian carcinoma. |
| title_full | New blocking antibodies impede adhesion, migration and survival of ovarian cancer cells, highlighting MFGE8 as a potential therapeutic target of human ovarian carcinoma. |
| title_fullStr | New blocking antibodies impede adhesion, migration and survival of ovarian cancer cells, highlighting MFGE8 as a potential therapeutic target of human ovarian carcinoma. |
| title_full_unstemmed | New blocking antibodies impede adhesion, migration and survival of ovarian cancer cells, highlighting MFGE8 as a potential therapeutic target of human ovarian carcinoma. |
| title_short | New blocking antibodies impede adhesion, migration and survival of ovarian cancer cells, highlighting MFGE8 as a potential therapeutic target of human ovarian carcinoma. |
| title_sort | new blocking antibodies impede adhesion migration and survival of ovarian cancer cells highlighting mfge8 as a potential therapeutic target of human ovarian carcinoma |
| url | http://europepmc.org/articles/PMC3745384?pdf=render |
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