Functional Folate Receptor Alpha Is Elevated in the Blood of Ovarian Cancer Patients

Abstract

BackgroundDespite low incidence, ovarian cancer is the fifth leading cause of cancer deaths and it has the highest mortality rate of all gynecologic malignancies among US women. The mortality rate would be reduced with an early detection marker. The folate receptor alpha (FRα) is one logical choice for a biomarker because of its prevalent overexpression in ovarian cancer and its exclusive expression in only a few normal tissues. In prior work, it was observed that patients with ovarian cancer had elevated serum levels of a protein that bound to a FRα-specific monoclonal antibody relative to healthy individuals. However, it was not shown that the protein detected was intact functional FRα. In the current study, the goal was to determine whether ovarian cancer patients (n = 30) had elevated serum levels of a fully functional intact FRα compared to matched healthy controls (n = 30).Methodology/Principal FindingsFRα levels in serum were analyzed by two methods, immunoblotting analysis and a radiolabeled folic acid-based microfiltration binding assay. Using the immunoassay, we observed that levels of FRα were higher in serum of ovarian cancer patients as compared to controls. Similar results were also observed using the microfiltration binding assay, which showed that the circulating FRα is functional. Importantly, we also found that the levels of FRα were comparable between early and advanced stage patients.ConclusionsOur results demonstrate that ovarian cancer patients have elevated levels of functional intact FRα. These findings support the potential use of circulating FRα as a biomarker of early ovarian cancer.

Folate receptor-α expression in resectable hepatic colorectal cancer metastases: patterns and significance

“…It binds and transports folic acid, and has recently emerged as a potential tumor biomarker. [5][6][7][8] Its expression in certain epithelial tumors such as ovarian, breast, endometrial and non-small cell lung carcinoma has been associated with tumor behavior. [9][10][11][12] Importantly, FRa expression is tumor specific, as it is significantly higher in tumor cells than in normal cells.…”

Increase in fr alpha expression in non-function pituitary adenomas

“…In the early stage of neoplasia, FRα could be overexpressed and result in stimulating the cells to repair the DNA that was damaged. Meanwhile, when the DNA undergoes more cell damage than it can repair, FRα will be continuously expressed and finally it will form a particular cellular environment that is beneficial to tumorigenesis and tumour progression (3). Some studies claim that the introduction of FRα into cells that normally do not express this receptor allows them to grow in low concentrations of folate (15,17) and form larger tumors when injected into nude mice (4).…”

Identification of a target protein of Hydra actinoporin-like toxin-1 (HALT-1) using GST affinity purification and SILAC-based quantitative proteomics

“…The folate receptor alpha is a GPI-anchored (glycosylphosphatidylinositol-anchored) membrane protein of 38-40 kDa that plays a major role in the uptake of folate/folic acid into cells via endocytosis (Luhrs and Slomiany 1989;Basal et al 2009). Folate receptor alpha is attached to the GPI anchor via its C-terminal end (Paulick and Bertozzi 2008;Maeda and Kinoshita 2011).…”