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转铁蛋白受体-1：在犬乳腺肿瘤中的表达及体外治疗应用

Transferrin Receptor-1: Expression in Canine Mammary Tumours and In Vitro Therapeutic Applications.

作者信息

Moccia Valentina, Rensi Nicolò, Marullo Giovanni Paolo, Sammarco Alessandro, Bonsembiante Federico, Torrigiani Filippo, Salvioni Lucia, Prosperi Davide, Zappulli Valentina, Cavicchioli Laura

机构信息

Department of Comparative Biomedicine, Health and Food Science, University of Padua, Legnaro, Italy.

Department of Animal Medicine, Production and Health, University of Padua, Legnaro, Italy.

出版信息

Vet Comp Oncol. 2025 Sep;23(3):476-485. doi: 10.1111/vco.70000. Epub 2025 Jun 23.

DOI:10.1111/vco.70000
PMID:40550706
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12378079/
Abstract

The transferrin receptor-1 (TFR-1) is overexpressed in many types of human cancers and, in recent years, several studies have investigated its use as a preferential channel for drug cellular uptake in cancer therapy. In veterinary medicine, TFR-1 expression in cancer cells and tissues has been poorly described, as well as its therapeutic potential. In this study we investigated TFR-1 expression in different subtypes of canine mammary tumours (CMTs) and in two CMT cell lines, one primary (CIPp) and one metastatic (CIPm). Additionally, we also compared the in vitro efficacy of an engineered human apoferritin nanocage loaded with doxorubicin (HFn(DOX)) with the conventional doxorubicin treatment on CIPp and CIPm. In CMT tissues, TFR-1 was more expressed in the tumoral tissues compared to the hyperplastic counterparts, specifically with regards to carcinoma and malignant myoepithelioma and simple carcinoma subtypes (p < 0.05). CIPp and CIPm did not show any significant difference in TFR-1 protein expression, while TFR-1 gene expression was higher in CIPm (p < 0.05). The treatment with HFn(DOX) was more efficient than free doxorubicin only on CIPp at high concentrations (50 μM). In conclusion, we show for the first time the variability of TFR-1 expression in CMT tissues and cell lines. Although further investigations are necessary, HFn can be loaded with different chemotherapeutic compounds, becoming an innovative therapeutic tool for the treatment of cancers highly expressing TFR-1 in veterinary and human medicine.

摘要

转铁蛋白受体-1（TFR-1）在多种人类癌症中过表达，近年来，多项研究探讨了其作为癌症治疗中药物细胞摄取的优先通道的用途。在兽医学中，癌细胞和组织中TFR-1的表达及其治疗潜力的描述较少。在本研究中，我们调查了犬乳腺肿瘤（CMT）不同亚型以及两种CMT细胞系（一种原代细胞系（CIPp）和一种转移细胞系（CIPm））中TFR-1的表达情况。此外，我们还比较了负载阿霉素的工程化人脱铁铁蛋白纳米笼（HFn(DOX)）与传统阿霉素治疗对CIPp和CIPm的体外疗效。在CMT组织中，与增生性对应组织相比，肿瘤组织中TFR-1的表达更高，特别是在癌、恶性肌上皮瘤和单纯癌亚型中（p < 0.05）。CIPp和CIPm在TFR-1蛋白表达上没有显著差异，而TFR-1基因表达在CIPm中更高（p < 0.05）。仅在高浓度（50 μM）时，HFn(DOX)处理对CIPp的效果比游离阿霉素更有效。总之，我们首次展示了CMT组织和细胞系中TFR-1表达的变异性。尽管还需要进一步研究，但HFn可以负载不同的化疗化合物，成为兽医学和人类医学中治疗高表达TFR-1癌症的创新治疗工具。

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