Department of Obstetrics and Gynecology, The First Affiliated Hospital of Yangtze University, 434023 Jingzhou, Hubei, China.
Department of Radiotherapy, Huabei Petroleum Administration Bureau General Hospital, 062550 Renqiu, Hebei, China.
Front Biosci (Landmark Ed). 2023 Aug 28;28(8):182. doi: 10.31083/j.fbl2808182.
As a spherical protein that acts as a repository for intracellular iron, Ferritin is the most important iron storage form and is known to influence tumor immunity. Unbound ferritin is composed of 24 subunits, made up of ferritin light chain (FTL) and ferritin heavy chain (FTH). Ferritin can be automatically put together to form hollow nanocages that measure 12 nm around the outside and 8 nm around the inside. Cancer causes the second-most deaths worldwide, effective elimination of tumor cells while protecting normal cells is the foundation of modern tumor therapy. To this end, the innate tumor-targeting activity of human FTH1, first identified ten years ago, is highly appealing. Unmodified human FTH1 binds to its receptor, transferrin receptor 1 (TfR1), which is frequently overexpressed in cancer cells. FTH1-TfR1 binding permits improved drug efficacy by promoting ferritin-mediated targeted delivery. In addition, FTH is also associated with the prognosis of multiple typies of cancer. The level of FTH1 is significantly and positively correlated with the infiltration of tumor-associated macrophages. FTH1 also plays an important role in regulating the tumor immunity of solid cancer. As such, FTH1 has been extensively applied in the targeted delivery of anticancer drugs, diagnostic molecules (e.g., radioisotopes and fluorophones), and inorganic nanoparticles (NPs) to tumors.This article reviews the role of FTH in cancer and its potential as a therapeutic target.
作为一种球形蛋白，它作为细胞内铁的储存库，铁蛋白是最重要的铁储存形式，并且已知会影响肿瘤免疫。无结合铁蛋白由 24 个亚基组成，由铁蛋白轻链（FTL）和铁蛋白重链（FTH）组成。铁蛋白可以自动组装成空心纳米笼，外部尺寸约为 12nm，内部尺寸约为 8nm。癌症是全球第二大致死原因，有效消除肿瘤细胞同时保护正常细胞是现代肿瘤治疗的基础。为此，十年前首次确定的人类 FTH1 的固有肿瘤靶向活性极具吸引力。未经修饰的人 FTH1 与受体转铁蛋白受体 1（TfR1）结合，TfR1 在癌细胞中经常过度表达。FTH1-TfR1 结合通过促进铁蛋白介导的靶向递送来提高药物疗效。此外，FTH 还与多种类型癌症的预后相关。FTH1 的水平与肿瘤相关巨噬细胞的浸润呈显著正相关。FTH1 在调节实体瘤的肿瘤免疫方面也起着重要作用。因此，FTH1 已广泛应用于抗癌药物、诊断分子（例如放射性同位素和荧光团）和无机纳米颗粒（NPs）向肿瘤的靶向递送。本文综述了 FTH 在癌症中的作用及其作为治疗靶点的潜力。
