Background/Objectives: Receptor for hyaluronan-mediated motility (RHAMM) is a hyaluronan (HA) receptor, which exerts diverse biological functions in not only physiological but also pathological conditions in human malignancies, including breast cancer. Although chemoresistance is a significant clinical challenge in breast cancer, a possible contribution of RHAMM and hyaluronan to breast cancer chemoresistance has remained unclear.Methods: We immunolocalized RHAMM and HA in breast carcinoma tissues. Also, we utilized epirubicin-sensitive (parental) and rpirubicin-resistant (EPIR) breast cancer cell lines to explore the role of RHAMMM in breast cancer progression.Results: We found out that RHAMM and HA were cooperatively correlated with breast cancer aggressiveness and recurrence after chemotherapy. In vitro studies demonstrated that RHAMM was overexpressed in EPIR cells compared to parental cells. In addition, the knockdown of RHAMM significantly suppressed proliferation and migration of both parental and EPIR cells. On the other hand, the expression level of cancer stem cell marker CD44, which was overexpressed in M-EPIR (epirubicin-resistant MCF-7 subline) compared to MCF-7, was significantly suppressed by knockdown of RHAMM. In addition, the knockdown of RHAMM significantly altered the expression of N-cadherin and E-cadherin, leading to an epithelial phenotype.Conclusions: Aberrant RHAMM signaling were considered to cause chemoresistance related to cancer stemness and epithelial to mesenchymal transition, and increased cell proliferation and migration of both chemo-sensitive and chemo-resistant breast cancer cells.
背景/目的：透明质酸介导运动受体（RHAMM）是一种透明质酸（HA）受体，不仅在生理状态下，也在包括乳腺癌在内的人类恶性肿瘤病理状态下发挥多种生物学功能。尽管化疗耐药是乳腺癌临床治疗中的重大挑战，但RHAMM与透明质酸对乳腺癌化疗耐药的可能作用机制尚不明确。方法：本研究对乳腺癌组织中的RHAMM与HA进行免疫定位分析，并利用表柔比星敏感型（亲代）与耐药型（EPIR）乳腺癌细胞系探究RHAMM在乳腺癌进展中的作用。结果：研究发现RHAMM与HA的表达协同关联乳腺癌侵袭性及化疗后复发风险。体外实验表明，与亲代细胞相比，EPIR细胞中RHAMM表达显著上调。RHAMM敲除能显著抑制亲代与EPIR细胞的增殖与迁移能力。值得注意的是，在表柔比星耐药亚系M-EPIR（相较于MCF-7）中过表达的肿瘤干细胞标志物CD44，其表达水平经RHAMM敲除后显著降低。此外，RHAMM敲除可显著改变N-钙黏蛋白与E-钙黏蛋白的表达模式，促使细胞向上皮表型转化。结论：异常RHAMM信号通路可能通过调控肿瘤干细胞特性及上皮-间质转化过程介导化疗耐药，同时增强化疗敏感与耐药乳腺癌细胞的增殖迁移能力。
Receptor for Hyaluronan Mediated Motility (RHAMM)/Hyaluronan Axis in Breast Cancer Chemoresistance
肿瘤(癌症)患者之家