Ali Khezrian, Ali Shojaeian, Armin Khaghani Boroujeni, Razieh Amini
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引用次数: 0
摘要
作为一种异质性疾病,乳腺癌(BC)的特点是乳腺上皮细胞不受控制的增殖。肿瘤微环境(TME)还包括炎症细胞、成纤维细胞、细胞外基质(ECM)和可溶性因子,它们都会促进乳腺癌的进展。从这个意义上说,巨噬细胞迁移抑制因子(MIF)是一种多向性促炎细胞因子,也是免疫反应的上游调节因子,它通过促进癌细胞增殖、存活、血管生成、侵袭、转移和干性,进而激活关键的致癌信号通路并诱导免疫抑制,从而增强乳腺肿瘤的发生。在此背景下,本综述旨在总结目前对 MIF 在癌症(尤其是 BC)中致病机制的认识,并探讨这种免疫调节细胞因子在信号通路和乳腺肿瘤发生中的核心作用。此外,还研究了不同的抑制剂,如小分子、抗体(Abs)或小干扰 RNA(siRNA)及其在 BC 研究中的抗肿瘤效果。以 MIF 为靶点的小分子和其他疗法。考虑到MIF是一个很有前景的治疗靶点,有必要对MIF靶向药物在BC患者中的应用进行进一步的临床评估。
Therapeutic Opportunities in Breast Cancer by Targeting Macrophage Migration Inhibitory Factor as a Pleiotropic Cytokine.
As a heterogeneous disease, breast cancer (BC) has been characterized by the uncontrolled proliferation of mammary epithelial cells. The tumor microenvironment (TME) also contains inflammatory cells, fibroblasts, the extracellular matrix (ECM), and soluble factors that all promote BC progression. In this sense, the macrophage migration inhibitory factor (MIF), a pleiotropic pro-inflammatory cytokine and an upstream regulator of the immune response, enhances breast tumorigenesis through escalating cancer cell proliferation, survival, angiogenesis, invasion, metastasis, and stemness, which then brings tumorigenic effects by activating key oncogenic signaling pathways and inducing immunosuppression. Against this background, this review was to summarize the current understanding of the MIF pathogenic mechanisms in cancer, particularly BC, and address the central role of this immunoregulatory cytokine in signaling pathways and breast tumorigenesis. Furthermore, different inhibitors, such as small molecules as well as antibodies (Abs) or small interfering RNA (siRNA) and their anti-tumor effects in BC studies were examined. Small molecules and other therapy target MIF. Considering MIF as a promising therapeutic target, further clinical evaluation of MIF-targeted agents in patients with BC was warranted.
期刊介绍:
Breast Cancer: Basic and Clinical Research is an international, open access, peer-reviewed, journal which considers manuscripts on all areas of breast cancer research and treatment. We welcome original research, short notes, case studies and review articles related to breast cancer-related research. Specific areas of interest include, but are not limited to, breast cancer sub types, pathobiology, metastasis, genetics and epigenetics, mammary gland biology, breast cancer models, prevention, detection, therapy and clinical interventions, and epidemiology and population genetics.