Assessment of folate receptor-β expression in human neoplastic tissues
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Jiayin Shen1, Karson S. Putt2, Daniel W. Visscher3, Linda Murphy4, Cynthia Cohen5, Sunil Singhal6, George Sandusky7, Yang Feng8, Dimiter S. Dimitrov8 and Philip S. Low1,2
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, 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
Philip S. Low, email:
Keywords: folate receptor, folate receptor beta, activated macrophage, tumor associated macrophage
Received: February 10, 2015 Accepted: March 03, 2015 Published: March 30, 2015
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.
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