Chen Xin, Wu Di, Zheng Yan, Liu Xingxing, Wang Jianmeng
Department of Radiology, The First Hospital of Jilin University, Changchun, China.
Department of Breast Surgery, The First Hospital of Jilin University, Changchun, China.
Front Pharmacol. 2020 Dec 10;11:598423. doi: 10.3389/fphar.2020.598423. eCollection 2020.
Prolactin receptor (PRLR) and growth hormone receptor (GHR) are closely related to the occurrence and development of breast cancer, and breast cancer cell endogenously express GHR, PRLR and GHR-PRLR heterodimer. In this case, the combined use of PRLR or GHR inhibitors may produce better anti-breast cancer potential than PRLR or GHR inhibitors alone. In this case, it is necessary to develop the dual-function GHR/PRLR antagonists with anti-breast cancer potential. For this, we used hybridoma technology to generate an anti-idiotypic antibody (termed H53). We then used various techniques, including competitive ELISA, competitive receptor binding analysis, and indirect immunofluorescence assay to identify H53, and the results show that H53 behaves as a typical internal image anti-idiotypic antibody (Ab2β). Further experiments indicate that H53 is a dual-function inhibitor, which not only inhibited PRLR-mediated intracellular signaling, but also blocked GHR-mediated intracellular signaling in a dose-dependent manner. Furthermore, H53 could inhibit PRL/GH-driven cancer cell proliferation and . This study indicates that H53 exhibits potential biological activity against breast tumors, which implies that internal image anti-idiotypic antibodies may be a useful strategy for the development of PRLR/GHR dual-function antagonists for breast cancer therapy.
催乳素受体（PRLR）和生长激素受体（GHR）与乳腺癌的发生发展密切相关，乳腺癌细胞内源性表达GHR、PRLR以及GHR-PRLR异二聚体。在此情况下，联合使用PRLR或GHR抑制剂可能比单独使用PRLR或GHR抑制剂具有更好的抗乳腺癌潜力。因此，有必要研发具有抗乳腺癌潜力的双功能GHR/PRLR拮抗剂。为此，我们利用杂交瘤技术制备了一种抗独特型抗体（命名为H53）。随后，我们运用多种技术，包括竞争性酶联免疫吸附测定、竞争性受体结合分析以及间接免疫荧光测定来鉴定H53，结果表明H53表现为典型的内影像抗独特型抗体（Ab2β）。进一步实验表明，H53是一种双功能抑制剂，它不仅能抑制PRLR介导的细胞内信号传导，还能以剂量依赖方式阻断GHR介导的细胞内信号传导。此外，H53能够抑制PRL/GH驱动的癌细胞增殖。本研究表明，H53对乳腺肿瘤具有潜在生物活性，这意味着内影像抗独特型抗体可能是开发用于乳腺癌治疗的PRLR/GHR双功能拮抗剂的一种有效策略。
