Immunohistochemical analysis of RHAMM expression in normal and neoplastic human tissues: a cell cycle protein with distinctive expression in mitotic cells and testicular germ cells.
Immunohistochemical analysis of RHAMM expression in normal and neoplastic human tissues: a cell cycle protein with distinctive expression in mitotic cells and testicular germ cells.
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DOI：
10.18632/oncotarget.24939
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发表时间：
2018-04-20
期刊：
影响因子：
--
通讯作者：
Du YN
中科院分区：
文献类型：
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作者：
Chen YT;Chen Z;Du YN
透明质酸介导的运动性受体 (RHAMM) 的表达会增加细胞运动性，而 RHAMM 过度表达会促进癌细胞的侵袭表型和转移。 RHAMM 已被建议作为多种肿瘤类型预后不良的生物标志物，包括肺癌、乳腺癌、结直肠癌、胃癌、胰腺导管癌和卵巢癌。 RNA研究表明RHAMM在正常组织中表达有限，但其在组织中的蛋白质表达数据有限。鉴于其作为预后标志物和治疗靶点的潜力，我们进行了免疫组织化学分析，以系统地表征正常和肿瘤人体组织中的 RHAMM 表达。在29个正常成人组织中，RHAMM蛋白表现出限制性表达，并在胸腺、淋巴结/扁桃体、小肠、结肠、皮肤、骨髓、胎盘和睾丸中观察到。 RHAMM 在这些正常组织中的细胞分布模式与 RHAMM 作为 G2/M 细胞周期蛋白一致，并且与另一种 G2/M 蛋白细胞周期蛋白 B2 的表达相比进一步支持了这一点。然而，与细胞周期蛋白 B2 的亚细胞定位不同，RHAMM 在后期和中期都修饰有丝分裂纺锤体。 RHAMM在肿瘤组织中的表达是可变的；一般来说，较高的 RHAMM 蛋白表达与组织学级别较高的肿瘤相关。与在体细胞组织中的表达不同，RHAMM 在成人睾丸生殖细胞的精母细胞阶段显示出弥漫性、强的、阶段特异性的表达。肿瘤对应物精细胞肿瘤也显示出强烈的 RHAMM 表达。睾丸中的这种独特表达表明 RHAMM 可能在正常睾丸生殖细胞成熟过程中发挥作用。
Expression of Receptor for Hyaluronic Acid Mediated Motility (RHAMM) increases cellular motility and RHAMM overexpression promotes invasive phenotype and metastasis of cancer cells. RHAMM has been suggested as a biomarker for poor prognosis in several tumor types, including lung, breast, colorectal, gastric, pancreatic ductal, and ovarian cancers. RNA studies showed restricted RHAMM expression in normal tissues, but its protein expression data in tissues were limited. In light of its potential as a prognostic marker and a therapeutic target, we performed immunohistochemical analysis to systematically characterize RHAMM expression in normal and neoplastic human tissues. Among 29 normal adult tissues, RHAMM protein showed restricted expression and was observed in the thymus, lymph node/tonsil, small intestine, colon, skin, bone marrow, placenta, and testis. The cellular distribution patterns of RHAMM in these normal tissues were consistent with RHAMM being a G2/M cell cycle protein, and this was further supported in comparison to the expression of cyclin B2, another G2/M protein. However, unlike the subcellular localization of cyclin B2, RHAMM decorated mitotic spindles in both anaphase and metaphase. RHAMM expression in tumor tissues is variable; and higher RHAMM protein expression is associated with histologically higher-grade tumors in general. Distinct from its expression in somatic tissues, RHAMM showed diffuse, strong, stage-specific expression in the spermatocyte stage of germ cells in adult testis. The neoplastic counterpart, spermatocytic tumor, also showed strong RHAMM expression. This unique expression in testis suggests that RHAMM may function during normal testicular germ cell maturation.