Increased RHAMM expression relates to ovarian cancer progression

Stephanie T Buttermore,Ambuj Kumar,Mitchel S Hoffman,Patricia A Kruk,Anne Champeaux,Santo V Nicosia

doi:10.1186/s13048-017-0360-1

Stephanie T Buttermore, Ambuj Kumar + Show 4 more

Open Access

https://doi.org/10.1186/s13048-017-0360-1

Copy DOI

Abstract

BackgroundElevated 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.ResultsDespite 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.ConclusionThis pilot study shows, for the first time, that RHAMM may contribute to OC disease and could potentially be used as a prognostic marker.

Highlights

Elevated hyaluronan-mediated motility receptor (RHAMM) has been reported to contribute to disease progression, aggressive phenotype and poor prognosis in multiple cancer types, Receptor for hyaluronan-mediated motility (RHAMM)’s role in ovarian cancer (OC) has not been elucidated
RHAMM is overexpressed in OC Immunological staining was performed on 41 tissue sections from 33 women
We found that 91% (20/22) of serous OC stained positively for RHAMM with levels of staining intensity ranging from weak (< 30% from each field, N = 4), moderate (30–50%, N = 7) to strong (> 50%, N = 9) while 0% (0/5) of normal ovarian surface epithelium (OSE) stained for RHAMM. (Fig. 1, Table 2) Staining patterns, as depicted by intense, punctate/diffuse cytoplasmic staining, seen in breast cancer (BC) positive control were consistent with previous reports of RHAMM in BC where intense staining is predominately in the cytoplasm and nucleus, but negative in the stroma [10, 11]

Summary

Introduction

Elevated hyaluronan-mediated motility receptor (RHAMM) has been reported to contribute to disease progression, aggressive phenotype and poor prognosis in multiple cancer types, RHAMM’s role in ovarian cancer (OC) has not been elucidated. OC lethality is largely due to ambiguous symptoms, emergence of drug resistance, disease reoccurrence and lack of reliable screening methods all leading to late stage diagnosis. Minimally expressed in normal tissue, elevated RHAMM in breast cancer (BC) and colorectal cancer (CRC) is associated with poor clinical outcome and more a aggressive

Methods

Results

Discussion

Conclusion