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Published on: August 2, 2024
Increased RHAMM expression relates to ovarian cancer progression
Stephanie T Buttermore1, Mitchel S Hoffman2, Ambuj Kumar3
1Department of Pathology & Cell Biology, University of South Florida, Morsani College of Medicine, 12901 Bruce B. Downs Blvd., MDC 11, Tampa, FL, 33612, USA.
Background:
Elevated hyaluronan-mediated motility receptor (RHAMM) has been reported to contribute to disease progression, aggressive phenotype and poor prognosis in multiple cancer types, however, RHAMM's role in ovarian cancer (OC) has not been elucidated. Therefore, we sought to evaluate the role for RHAMM in epithelial OC.
Results:
Despite little to no expression in normal ovarian surface epithelium, western immunoblotting, immunohistochemical staining and enzyme linked immunosorbent assay showed elevated RHAMM levels in clinical tissue sections, omental metastasis and urine specimens of serous OC patients, as well as in cell lysates. We also found that RHAMM levels increase with increasing grade and stage in serous OC tissues and that RHAMM localizes to the apical cell surface and inclusion cysts. Apical localization of RHAMM suggested protein secretion which was validated by detection of significantly elevated urinary RHAMM levels (p < 0.0001) in OC patients (116.66 pg/mL) compared with normal controls (8.16 pg/mL). Likewise, urinary RHAMM levels decreased following cytoreductive surgery in OC patients suggesting the source of urinary RHAMM from tumor tissue. Lastly, we validated RHAMM levels in OC cell lysate and found at least 12× greater levels compared to normal ovarian surface epithelial cells.
Conclusion:
This pilot study shows, for the first time, that RHAMM may contribute to OC disease and could potentially be used as a prognostic marker.
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