Cholangiocarcinoma (CCA) represents the second most common primary hepatic malignancy and originates from the neoplastic transformation of the biliary cells. The intrahepatic subtype includes two morpho-molecular forms: large-duct type intrahepatic CCA (iCCA) and small-duct type iCCA. Iron is fundamental for the cellular processes, contributing in tumor development and progression. The aim of this study was to evaluate iron uptake, storage, and efflux proteins in both lipopolysaccharide-inflamed small and large cholangiocytes as well as in different iCCA subtypes. Our results show that, despite an increase in interleukin-6 production by both small and large cholangiocytes, ferroportin (Fpn) was decreased only in small cholangiocytes, whereas transferrin receptor-1 (TfR1) and ferritin (Ftn) did not show any change. Differently from in vitro models, Fpn expression was increased in malignant cholangiocytes of small-duct type iCCA in comparison to large-duct type iCCA and peritumoral tissues. TfR1, Ftn and hepcidin were enhanced, even if at different extent, in both malignant cholangiocytes in comparison to the surrounding samples. Lactoferrin was higher in large-duct type iCCA in respect to small-duct type iCCA and peritumoral tissues. These findings show a different iron handling by inflamed small and large cholangiocytes, and small and large-duct type iCCA. The difference in iron homeostasis by the iCCA subtypes may have implications for the tumor management.

胆管癌（CCA）代表第二常见的原发性肝恶性肿瘤，起源于胆管细胞的肿瘤转化。肝内亚型包括两种形态分子形式：大管型肝内CCA（iCCA）和小管型iCCA。铁是细胞过程的基础，有助于肿瘤的发展和发展。这项研究的目的是评估脂多糖刺激的大小胆管细胞以及不同iCCA亚型中铁的吸收，储存和流出蛋白。我们的结果表明，尽管小胆管细胞和大胆管细胞都增加了白介素6的产生，但仅小胆管细胞中铁转运蛋白（Fpn）的表达降低了，而转铁蛋白受体1（TfR1）和铁蛋白（Ftn）的变化却没有。与体外模型不同，与大管型iCCA和肿瘤周围组织相比，小管型iCCA的恶性胆管细胞中Fpn表达增加。与周围样品相比，两种恶性胆管细胞中的TfR1，Ftn和铁调素均得到增强，即使程度不同。相对于小管型iCCA和肿瘤周围组织，乳铁蛋白在大管型iCCA中更高。这些发现表明，发炎的小胆管和大胆管细胞以及小管和大管型iCCA对铁的处理方式不同。iCCA亚型在铁稳态中的差异可能对肿瘤的治疗有影响。与周围的样品相比，两种恶性胆管细胞中的浓度都高。相对于小管型iCCA和肿瘤周围组织，乳铁蛋白在大管型iCCA中更高。这些发现表明，发炎的小胆管和大胆管细胞以及小管和大管型iCCA对铁的处理方式不同。iCCA亚型在铁稳态中的差异可能对肿瘤的治疗有影响。与周围的样品相比，两种恶性胆管细胞中的浓度都高。相对于小管型iCCA和肿瘤周围组织，乳铁蛋白在大管型iCCA中更高。这些发现表明，发炎的小胆管和大胆管细胞以及小管和大管型iCCA对铁的处理方式不同。iCCA亚型在铁稳态中的差异可能对肿瘤的治疗有影响。