Increased RHAMM expression relates to ovarian cancer progression.
Increased RHAMM expression relates to ovarian cancer progression.
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DOI：
10.1186/s13048-017-0360-1
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发表时间：
2017-09-27
影响因子：
4
通讯作者：
Kruk PA
中科院分区：
文献类型：
--
作者：
Buttermore ST;Hoffman MS;Kumar A;Champeaux A;Nicosia SV;Kruk PA
透明质酸介导的运动受体（RHAMM）的升高已被报道有助于多种癌症类型的疾病进展，侵袭性表型和预后不良，然而，RHAMM在卵巢癌（OC）中的作用尚未阐明。因此，我们试图评估RHAMM在上皮OC中的作用。尽管在正常卵巢表面上皮中几乎没有表达，但Western免疫印迹、免疫组化染色和酶联免疫吸附试验显示，在浆液性OC患者的临床组织切片、网膜转移和尿液标本以及细胞裂解物中RHAMM水平升高。我们还发现RHAMM水平随着浆液性OC组织的级别和分期的增加而增加，并且RHAMM定位于顶端细胞表面和包涵体囊肿。RHAMM的顶端定位提示蛋白质分泌，这通过检测OC患者（116.66 pg/mL）与正常对照（8.16 pg/mL）相比显著升高的尿RHAMM水平（p < 0.0001）来验证。同样，尿RHAMM水平降低后，细胞减灭术在OC患者表明尿RHAMM来源于肿瘤组织。最后，我们验证了OC细胞裂解物中的RHAMM水平，发现与正常卵巢表面上皮细胞相比，RHAMM水平至少高出12倍。这项初步研究首次表明，RHAMM可能有助于OC疾病，并可能被用作预后标志物。
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. 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. 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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