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In veterinary oncology, its expression pattern in canine mammary tumours and the therapeutic value of TFR-1 targeting remain limited. This study assessed TFR-1 in canine mammary tumour tissues and two cell lines (primary and metastatic) and compared doxorubicin alone with an engineered human apoferritin nanocage loaded with doxorubicin (HFn(DOX)) in vitro. TFR-1 was higher in tumours than hyperplastic tissues for specific subtypes, with differential gene versus protein expression between cell lines. HFn(DOX) improved efficacy over free doxorubicin on the primary line at higher dose. Overall, results show TFR-1 variability and support apoferritin nanocages as a potential TFR-1-targeted therapeutic tool.",{"@graph":69,"@context":126},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/transferrin-receptor-1-expression-in-canine-mammary-tumours-and-in-vitro-therapeutic-applications/374725/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/transferrin-receptor-1-expression-in-canine-mammary-tumours-and-in-vitro-therapeutic-applications/374725.png","ImageObject",300,407,{"name":92,"@type":93},"eBook King","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118,122],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main purpose of the study on TFR-1 in canine mammary tumours?","Question",{"text":112,"@type":113},"To investigate how TFR-1 is expressed across canine mammary tumour tissues and two related cell lines, and to evaluate an in vitro TFR-1-targeted treatment strategy using an apoferritin nanocage loaded with doxorubicin.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did TFR-1 expression differ between canine tumour tissues and hyperplastic counterparts?",{"text":117,"@type":113},"TFR-1 was more expressed in tumoral tissues than in hyperplastic tissues, particularly for carcinoma and malignant myoepithelioma and simple carcinoma subtypes (p \u003C 0.05).",{"name":119,"@type":110,"acceptedAnswer":120},"How did HFn(DOX) perform compared with free doxorubicin in vitro?",{"text":121,"@type":113},"HFn(DOX) was more efficient than free doxorubicin only on the primary cell line (CIPp) at high concentrations (50 μM).",{"name":123,"@type":110,"acceptedAnswer":124},"What conclusion does the study draw about using apoferritin nanocages for TFR-1-high cancers?",{"text":125,"@type":113},"The study demonstrates variability of TFR-1 expression in canine tumour tissues and cell lines and suggests that apoferritin nanocages could be loaded with different chemotherapeutic compounds for treating cancers with high TFR-1 expression, pending further investigation.","https://schema.org",{"og:url":83,"og:type":128,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":130,"canonical":83},"index,follow",{"doc_id":132,"site_id":62},374725,1790269355,{"code":4,"msg":5,"data":135},{"doc_id":132,"user_id":136,"nickname":92,"user_avatar":137,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":138,"file_id":139,"file_url":140,"file_type":141,"file_size":142,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"language":143,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":144,"faqs":145,"seo_title":146,"seo_description":67,"update_tm":147,"read_time":148},962088006270,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","Veterinary and Comparative Oncology  \nORIGINAL ARTICLE  OPEN ACCESS   \nTransferrin Receptor-1: Expression in Canine Mammary Tumours and In Vitro Therapeutic Applications  \nValentina Moccia1  | Nicolò Rensi1 | Giovanni Paolo Marullo1 | Alessandro Sammarco1  | Federico Bonsembiante2 | Filippo Torrigiani1 | Lucia Salvioni3 | Davide Prosperi3 | Valentina Zappulli1 | Laura Cavicchioli1  \n1Department of Comparative Biomedicine, Health and Food Science, University of Padua, Legnaro, Italy | 2Department of Animal Medicine, Production and Health, University of Padua, Legnaro, Italy | 3Department of Biotechnologies and Biosciences, University of Milan Bicocca, Milano, Italy Correspondence: Valentina Moccia ([valentina.moccia@phd.unipd.it](valentina.moccia@phd.unipd.it))  \nReceived: 19 February 2025 | Revised: 3 June 2025 | Accepted: 4 June 2025  \nFunding: The authors received no specific funding for this work.  \nKeywords: apoferritin nanocage | canine mammary cancer | doxorubicin  \nABSTRACT  \nThe 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 \u003C 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 \u003C 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.  \n1 | Introduction  \nTransferrin receptors (TFRs) are transmembrane glycoproteins that allow the internalisation of iron into cells after binding to transferrin (TF), an iron-carrier protein [1–3] . TFR-1 is expressed in all cells, except mature erythrocytes, and its expression increases with the cell requirement for iron [2–4] . Since iron is necessary for cell proliferation and DNA synthesis, TFR-1 expression increases in highly proliferating cells, such as cancer cells [4] . Particularly, TFR-1 is often overexpressed in human cancer cells, and its high expression has been associated with higher malignancy, advanced  \nstage, poorer prognosis, and tumour recurrence in different types of human cancers [4, 5] . More than 40 years ago, TFR-1 was demonstrated to be particularly upregulated in tissues of human breast cancer (HBC), the most common neoplasia in women [6–8] . Therefore, considering the high expression, the easy accessibility on the cell surface and the dynamics of receptor internalisation after ligand engagement, TFR-1 has been investigated in several studies on specific anticancer therapies in human medicine [5] . In HBC, both preclinical and clinical studies have examined its therapeutic potential, aiming to overcome drug resistance and adverse toxicity of chemotherapeutics [9, 10] . Throughout the years, different  \nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, d","cbCaim5OT4vuu2K8","https://ap.wps.com/l/cbCaim5OT4vuu2K8","pdf",1036756,"English","# Introduction\n## TFR-1 as a cancer-associated iron uptake receptor\n## Previous therapeutic targeting in human medicine\n## Rationale for studying TFR-1 in veterinary oncology\n## Engineered apoferritin nanocage drug delivery","[{\"question\":\"What is the main purpose of the study on TFR-1 in canine mammary tumours?\",\"answer\":\"To investigate how TFR-1 is expressed across canine mammary tumour tissues and two related cell lines, and to evaluate an in vitro TFR-1-targeted treatment strategy using an apoferritin nanocage loaded with doxorubicin.\"},{\"question\":\"How did TFR-1 expression differ between canine tumour tissues and hyperplastic counterparts?\",\"answer\":\"TFR-1 was more expressed in tumoral tissues than in hyperplastic tissues, particularly for carcinoma and malignant myoepithelioma and simple carcinoma subtypes (p \\u003c 0.05).\"},{\"question\":\"How did HFn(DOX) perform compared with free doxorubicin in vitro?\",\"answer\":\"HFn(DOX) was more efficient than free doxorubicin only on the primary cell line (CIPp) at high concentrations (50 μM).\"},{\"question\":\"What conclusion does the study draw about using apoferritin nanocages for TFR-1-high cancers?\",\"answer\":\"The study demonstrates variability of TFR-1 expression in canine tumour tissues and cell lines and suggests that apoferritin nanocages could be loaded with different chemotherapeutic compounds for treating cancers with high TFR-1 expression, pending further investigation.\"}]","Transferrin Receptor-1: Expression in Canine Mammary Tumours and In Vitro Therapeutic Applications | PDF",1790202266,25]