Assessment of folate receptor-β expression in human neoplastic tissues.

Jiayin Shen, Karson S Putt, Daniel W Visscher, Linda Murphy, Cynthia Cohen, Sunil Singhal, George Sandusky, Yang Feng, Dimiter S Dimitrov, Philip S Low

Journal: Oncotarget 2016;6(16):14700-9

PMID: 25909292

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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.

Address: Department of Chemistry, Purdue University, West Lafayette, IN, USA.; Center for Drug Discovery, Purdue University, West Lafayette, IN, USA.; Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA.; Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA.; Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, GA, USA.; Division of Thoracic Surgery, Department of Surgery, Hospital of the University of Pennsylvania School of Medicine, Philadelphia, PA, USA.; Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA.; 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.; Department of Chemistry, Purdue University, West Lafayette, IN, USA.; Center for Drug Discovery, Purdue University, West Lafayette, IN, USA.

DOI: 10.18632/oncotarget.3739

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MeSH Terms: Female, Folate Receptor 2, Humans, Macrophages, Male, Neoplasms