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.
Highlights
Folic acid is required for one-carbon metabolism, which is involved in de novo synthesis of nucleotides, methylation of DNA, carboxymethylation of G proteins and synthesis of many important metabolic intermediates [1]
We report here that folate receptor (FR)-β positive tumor associated macrophage-like cells are present in most human cancers and that several human malignancies that derive from FR-β negative cells express the β isoform of FR
To ensure that attachment of biotin to m909 did not compromise selectivity of the antibody for FRβ, binding of biotinylated-m909 was compared with CHO-K1 cells that do not express either FR-α or FR-β [26], CHO-K1 cells transfected with a stable human FR-β expression vector and KB cells that naturally express high levels of FR-α, but not FR-β [27]
Summary
Folic acid (vitamin B9) is required for one-carbon metabolism, which is involved in de novo synthesis of nucleotides, methylation of DNA, carboxymethylation of G proteins and synthesis of many important metabolic intermediates [1]. Folic acid is taken into cells via the reduced folate carrier [2], the proton coupled folate transporter [3] or one of four isoforms (α, β, γ, δ) of the folate receptor (FR) [4]. FR’s 104-fold higher affinity for folate (Kd ~ 10-10 M) may render the receptor the preferred pathway for uptake of the vitamin when folate concentrations are low, the restricted expression of FR and its general inaccessibility in normal tissues may limit this potential benefit to very few cells [5]. FR-α is expressed primarily on the apical surfaces of epithelial cells lining the openings in the lungs, kidneys, mammary ducts and choroid plexus, where it only encounters folates within the respective lumens [6, 7, 8]. FR-γ may be secreted in very low quantities into the bloodstream where it is difficult to detect [12, 13], and FR-δ has only been observed on regulatory T cells and ova [14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
