Gallo Valentina, Antonini Giovanni
Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, Rome 00146, Italy.
Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, Rome 00146, Italy; National Institute of Biostructures and Biosystems (INBB), Via dei Carpegna 19, Rome 00165, Italy.
Biomed Pharmacother. 2024 Dec;181:117743. doi: 10.1016/j.biopha.2024.117743. Epub 2024 Dec 10.
Lactoferrin (Lf) is a positively charged iron-binding glycoprotein that has piqued the scientific community's interest due to its pleiotropic behavior, exhibiting a wide range of biological activities, including antimicrobial, antioxidant, anti-inflammatory, immunomodulatory, and anticancer effects. This narrative review explores the current understanding of Lf's role in cancer, focusing on the endogenously expressed human full-length and ΔLf isoforms, and the effects of treatment with exogenous human and bovine Lf. We evaluated and compared the mechanisms by which Lf influences tumorigenesis and cancer progression, focusing on its impact on key processes such as cell growth, apoptosis, angiogenesis, cell migration, and invasiveness. Notably, the mechanisms of action of human and bovine Lf show some divergences, presumably due to slight structural differences that may lead to opposing effects. Insights from this comparison may help identify new Lf variants with enhanced anticancer activity. Indeed, both human and bovine Lf showed substantial anticancer activity, prompting researchers to investigate their potential utility in cancer prevention and progression. However, some studies have indicated that high levels of human Lf expression may be linked to increased carcinogenesis and metastasis, reflecting its intricate and context-dependent role in cancer. Thus, we emphasize the need for a deeper comprehension of Lf biology and its regulation to enhance understanding of Lf's role in cancer and identify more targeted therapeutic strategies, encouraging further research in this area.
乳铁蛋白（Lf）是一种带正电荷的铁结合糖蛋白，因其多效性而引起了科学界的兴趣，它具有广泛的生物活性，包括抗菌、抗氧化、抗炎、免疫调节和抗癌作用。这篇叙述性综述探讨了目前对Lf在癌症中作用的理解，重点关注内源性表达的人类全长和ΔLf异构体，以及外源性人类和牛Lf治疗的效果。我们评估并比较了Lf影响肿瘤发生和癌症进展的机制，重点关注其对细胞生长、凋亡、血管生成、细胞迁移和侵袭等关键过程的影响。值得注意的是，人类和牛Lf的作用机制存在一些差异，可能是由于细微的结构差异导致相反的效果。这种比较的见解可能有助于识别具有增强抗癌活性的新Lf变体。事实上，人类和牛Lf都显示出显著的抗癌活性，促使研究人员研究它们在癌症预防和进展中的潜在用途。然而，一些研究表明，高水平的人类Lf表达可能与致癌作用和转移增加有关，这反映了其在癌症中复杂且依赖于背景的作用。因此，我们强调需要更深入地理解Lf生物学及其调控，以增进对Lf在癌症中作用的理解，并确定更有针对性的治疗策略，鼓励在这一领域进行进一步研究。
