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. 2013 Aug 16;8(8):e72708. doi: 10.1371/journal.pone.0072708. eCollection 2013.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Blocking / pharmacology*
  • Antigens, Surface / immunology*
  • Antigens, Surface / 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*
  • Milk Proteins / metabolism
  • Molecular Targeted Therapy*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology*
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology


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

Grant support

This work was supported by Institut Curie, INSERM, Association pour La Recherche contre le Cancer, a prize from Fondation de France, and a two-years collaboration contract between Institut Curie, INSERM, and ThromboGenics NV, Leuven, Belgium ( ThromboGenics NV outlined the strategy for antibody generation, performed the mice immunization, checked the specificity of the new anti-human MFGE8 antibodies, sequenced their variable regions, and participated in the design of the tests for selection of the lead candidate antibodies.