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: 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
• Journal: PloS one (PLoS One) Vol. 8 Issue 8 Pg. e72708 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23977342 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Blocking
• Antigens, Surface
• MFGE8 protein, human
• Milk Proteins

Topics

• Animals
• Antibodies, Blocking (pharmacology)
• Antigens, Surface (immunology, metabolism)
• Biological Assay
• Biopsy
• Cell Adhesion (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Survival (drug effects)
• Female
• Humans
• Mice
• Milk Proteins (immunology, metabolism)
• Molecular Targeted Therapy
• Ovarian Neoplasms (drug therapy, pathology)
• Triple Negative Breast Neoplasms (metabolism, pathology)