Department of Immunology, Guilin Medical University, Guilin, Guangxi province, China.
Department of Pathology, Guilin Medical University Affiliated Hospital, Guilin, Guangxi province, China.
Bioengineered. 2022 Apr;13(4):10072-10087. doi: 10.1080/21655979.2022.2063593.
The incidence rate of breast cancer is the highest in the world, and major problem in the clinical treatment is the therapy resistance of breast cancer stem cells (CSCs). Thus, new therapeutic approaches targeting breast CSCs are needed. Our previous study demonstrated cancer-derived sialylated IgG (SIA-IgG) is highly expressed in cancer cells with stem/progenitor features. Furthermore, a high frequency of SIA-IgG in breast cancer tissue predicted metastasis and correlated with poor prognosis factors, and depletion of IgG in breast cancer leads to lower malignancy of cancer cells, suggesting SIA-IgG could be a potential therapeutic target in breast cancer. In this study, we first investigated the relationship of SIA-IgG expression with the clinicopathological characteristics and clinical prognosis of breast carcinoma patients, and the data confirmed that the expression of SIA-IgG confers poor prognosis in breast cancer. Successively, by using a monoclonal antibody specifically against SIA-IgG, we targeted SIA-IgG on the surface of MDA-MB-231 cells and detected their functional changes, and the results suggested SIA-IgG to be a promising antibody therapeutic target in breast cancer. In addition, we explored the mechanism of action at the molecular level of SIA-IgG on breast cancer cell, the findings suggest that SIA-IgG promotes proliferation, metastasis, and invasion of breast cancer cells through the /β-catenin signaling pathway. Developing therapeutic antibody needs effective therapeutic target, and the antibody should better be a monoclonal antibody with high affinity and high specificity. This study provides a potential prognostic marker and a novel therapeutic target for breast cancer.
乳腺癌的发病率居全球之首，其临床治疗的主要问题是乳腺癌干细胞（CSC）的治疗耐药性。因此，需要针对乳腺癌 CSC 的新治疗方法。我们之前的研究表明，癌症衍生的唾液酸化 IgG（SIA-IgG）在具有干细胞/祖细胞特征的癌细胞中高度表达。此外，乳腺癌组织中 SIA-IgG 的高频率预示着转移，并与不良预后因素相关，而乳腺癌中 IgG 的耗竭会降低癌细胞的恶性程度，表明 SIA-IgG 可能是乳腺癌的潜在治疗靶点。在这项研究中，我们首先研究了 SIA-IgG 表达与乳腺癌患者临床病理特征和临床预后的关系，数据证实 SIA-IgG 的表达赋予乳腺癌不良预后。随后，我们使用一种针对 SIA-IgG 的单克隆抗体，靶向 MDA-MB-231 细胞表面的 SIA-IgG，并检测其功能变化，结果表明 SIA-IgG 是乳腺癌有前途的抗体治疗靶点。此外，我们还在分子水平上探讨了 SIA-IgG 对乳腺癌细胞作用的机制，研究结果表明 SIA-IgG 通过/β-catenin 信号通路促进乳腺癌细胞的增殖、转移和侵袭。开发治疗性抗体需要有效的治疗靶点，而该抗体最好是具有高亲和力和高特异性的单克隆抗体。本研究为乳腺癌提供了一个潜在的预后标志物和一个新的治疗靶点。
