Expression of transferrin receptor‐1 (TFR‐1) in canine osteosarcomas

Abstract

Due to high rates of proliferation and DNA synthesis, neoplastic cells have higher requirements of iron than normal cells. For that reason, neoplastic cells have remodelled iron metabolism pathways, over‐expressing genes encoding for iron uptake proteins, among which Transferrin Receptor‐1 (TFR‐1). Accumulating evidence has proven that overexpression of TFR‐1 and high Iron concentration, are both widespread condition of cancer cells, both essential to tumour onset and progression. We studied TFR‐1 and PCNA immunohistochemical expression in fifteen (15) Canine osteoblastic osteosarcomas (COS). After immunohistochemical staining, counting of TFR‐1 positive cells by two independent observers showed that 85%–95% of neoplastic cells were strongly labelled at cytoplasmic level by anti‐TFR‐1 antibody in all examined COS. Furthermore, 70%–80% of neoplastic cells were positively labelled at the nuclear level by PCNA. Surprisingly, about 100% of intratumour vascular endothelial cells were also positive, whereas extratumour vascular endothelial cells were negative. The latter is an interesting finding, as TFR‐1 is usually not expressed in normal vasculature, with the exception of normal brain vascular endothelium, where it allows transport of transferrin, and thus iron, into tissues, suggesting a similar function here to support cancer growth. The early results presented highlight the relevance of TFR‐1 expression in canine OS, suggesting therapies involving both TFR‐1 and Iron metabolisms in dogs with osteosarcoma should be developed.

Enhanced Cellular Uptake of H-Chain Human Ferritin Containing Gold Nanoparticles

“…In summary, we show that cellular ferritin uptake seems to The differences in uptake between both homopolymers, FTH and FTL, containing either AuNP or iron oxides, can be attributed to the availability of their uptake receptors. H-chains are mainly internalized by transferrin receptor 1 (TR1), which is ubiquitously expressed and overexpressed in cancerous and vascular endothelial cell lines [64]. On the other hand, L-chains are internalized by the SCARA5 receptor, which is less abundant in cells and only expressed in particular cell types [39,65].…”

Cytotoxicity of an Innovative Pressurised Cyclic Solid–Liquid (PCSL) Extract from Artemisia annua

“…However, canine and human osteosarcomas, in line with cancer cells hallmarks, are also known to overexpress membrane transferrin receptors, which make cells particularly susceptible to a particular form of iron-dependent non-apoptotic cell death, known as Ferroptosis, the latter of which is activated by artemisinin [34]. It is, therefore, possible that the phytochemicals present in the PCSL extract of A. annua activate multiple molecular cell death pathways in cancer cells.…”

Progress in Delivery of siRNA-Based Therapeutics Employing Nano-Vehicles for Treatment of Prostate Cancer

“…In previous sections, we demonstrated that the surface modification of nanoparticles by PSMA increases their capability in targeting PC cells. It is worth mentioning that transferrin (Tf) ligands can be implemented for selectively targeting PCa cells, as they are upregulated in PCa cells [ 248 , 249 , 250 ]. Gold nanoparticles can target the Tf receptors on PCa cells to deliver siRNA to PCa cells, resulting in an inhibition of RelA (up to 35%) and a diminution in the growth and survival of cancer cells [ 251 ].…”