Assessment of folate receptor-β expression in human neoplastic tissues

  • Oncotarget. 2015 Jun 10;6(16):14700-9. doi: 10.18632/oncotarget.3739.
Jiayin Shen  1 ,  Karson S Putt  2 ,  Daniel W Visscher  3 ,  Linda Murphy  4 ,  Cynthia Cohen  5 ,  Sunil Singhal  6 ,  George Sandusky  7 ,  Yang Feng  8 ,  Dimiter S Dimitrov  8 ,  Philip S Low  1  2
Affiliations
  • 1. Department of Chemistry, Purdue University, West Lafayette, IN, USA.
  • 2. Center for Drug Discovery, Purdue University, West Lafayette, IN, USA.
  • 3. Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA.
  • 4. Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA.
  • 5. Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, GA, USA.
  • 6. Division of Thoracic Surgery, Department of Surgery, Hospital of the University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
  • 7. Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA.
  • 8. Protein Interactions Section, Laboratory of Experimental Immunology, Cancer and Inflammation Program, Center for Cancer, National Cancer Institute-Frederick, National Institutes of Health, Frederick, MD, USA.
PMID: 25909292 DOI: 10.18632/oncotarget.3739
Abstract

Over-expression of folate receptor Alpha on Cancer cells has been frequently exploited for delivery of folate-targeted imaging and therapeutic agents to Tumors. Because limited information exists on expression of the beta isoform of the folate receptor in human cancers (FR-β), we have evaluated the immunohistochemical staining pattern of FR-β in 992 tumor sections from 20 different human Cancer types using a new anti-human FR-β monoclonal antibody. FR-β expression was shown to be more pronounced in cells within the stroma, primarily Macrophages and macrophage-like cells than Cancer cells in every Cancer type studied. Moreover, FR-β expression in both Cancer and stromal cells was found to be statistically more prominent in females than males. A significant positive correlation was also observed between FR-β expression on stromal cells and both the stage of the Cancer and the presence of lymph node metastases. Based on these data we conclude FR-β may constitute a good target for specific delivery of therapeutic agents to activated Macrophages and that accumulation of FR-β positive Macrophages in the stroma could serve as a useful indicator of a tumor's metastatic potential.

Keywords
activated macrophage; folate receptor; folate receptor beta; tumor associated macrophage.