title: New blocking antibodies impede adhesion, migration and survival of ovarian cancer cells, highlighting MFGE8 as a potential therapeutic target of human ovarian carcinoma.
abstract: 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.
authors: Institut Curie, Centre de Recherche, Paris, France.
authors: Lorenzo
authors: L
authors: Tibaldi
authors: Shirley
authors: S
authors: Leyman
authors: André
authors: A
authors: Nicolas
authors: Sofie
authors: S
authors: Notebaert
authors: Melissa
authors: M
authors: Dewulf
authors: Thu Hoa
authors: TH
authors: Ngo
authors: Claudia
authors: C
authors: Zuany-Amorim
authors: Nathalie
authors: N
authors: Amzallag
authors: Isabelle
authors: I
authors: Bernard-Pierrot
authors: Xavier
authors: X
authors: Sastre-Garau
authors: Clotilde
authors: C
authors: Théry
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology*; D000954:Antigens, Surface / Q000276:immunology* / Q000378:metabolism; D001681:Biological Assay; D001706:Biopsy; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D008894:Milk Proteins / Q000276:immunology* / Q000378:metabolism; D058990:Molecular Targeted Therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: D019138:Antibodies, Blocking; D000954:Antigens, Surface; C098942:MFGE8 protein, human; D008894:Milk Proteins
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