Department of Gynecology and Gynecologic Oncology, Medical University of Bialystok, 15-089 Bialystok, Poland.
University Oncology Center, University Clinical Hospital in Bialystok, 15-276 Bialystok, Poland.
Molecules. 2022 Mar 22;27(7):2041. doi: 10.3390/molecules27072041.
Endometrial cancer (EC) is one of the most frequent female malignancies. Because of a characteristic symptom, vaginal bleeding, EC is often diagnosed in an early stage. Despite that, some EC cases present an atypical course with rapid progression and poor prognosis. There have been multiple studies conducted on molecular profiling of EC in order to improve diagnostics and introduce personalized treatment. Chemokines-a protein family that contributes to inflammatory processes that may promote carcinogenesis-constitute an area of interest. Some chemokines and their receptors present alterations in expression in tumor microenvironment. CXCL12, which binds the receptors CXCR4 and CXCR7, is known for its impact on neoplastic cell proliferation, neovascularization and promotion of epidermal-mesenchymal transition. The CCL2-CCR2 axis additionally plays a pivotal role in EC with mutations in the LKB1 gene and activates tumor-associated macrophages. CCL20 and CCR6 are influenced by the RANK/RANKL pathway and alter the function of lymphocytes and dendritic cells. Another axis, CXCL10-CXCR3, affects the function of NK-cells and, interestingly, presents different roles in various types of tumors. This review article consists of analysis of studies that included the roles of the aforementioned chemokines in EC pathogenesis. Alterations in chemokine expression are described, and possible applications of drugs targeting chemokines are reviewed.
子宫内膜癌 (EC) 是女性最常见的恶性肿瘤之一。由于其特征性症状，阴道出血，EC 通常在早期被诊断出来。尽管如此，一些 EC 病例表现出非典型的病程，进展迅速，预后不良。已经有多项关于 EC 分子谱的研究旨在提高诊断并引入个性化治疗。趋化因子是一组参与炎症过程的蛋白质，可能促进致癌作用，这是一个研究热点。一些趋化因子及其受体在肿瘤微环境中的表达发生改变。CXCL12 与受体 CXCR4 和 CXCR7 结合，其对肿瘤细胞增殖、新生血管形成和促进表皮间充质转化具有重要作用。CCL2-CCR2 轴在 LKB1 基因突变的 EC 中也起着关键作用，激活肿瘤相关巨噬细胞。CCL20 和 CCR6 受 RANK/RANKL 通路的影响，改变淋巴细胞和树突状细胞的功能。另一个轴，CXCL10-CXCR3，影响 NK 细胞的功能，有趣的是，在不同类型的肿瘤中具有不同的作用。这篇综述文章分析了包括上述趋化因子在 EC 发病机制中的作用的研究。描述了趋化因子表达的改变，并回顾了靶向趋化因子的药物的可能应用。
