Blocking transferrin receptor inhibits the growth of lung adenocarcinoma cells in vitro

Wu, Yihe; Xu, Jun; Chen, Jinbo; Zou, Meirong; Rusidanmu, Aizemaiti; Yang, Rong

doi:10.1111/1759-7714.12572

Cited by 20 publications

(6 citation statements)

References 43 publications

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“…The 2 −ΔCT method was used to determine the expression level of all messenger RNAs (mRNAs) (17). One-way analysis of variance was used for comparisons among three groups, and a P value <0.05 was considered statistically significant.…”

Section: Discussionmentioning

confidence: 99%

Identification of key pathways and core genes involved in atherosclerotic plaque progression

Yang

Yao

et al. 2021

Ann Transl Med

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Background: Atherosclerosis leads to the occurrence of cardiovascular diseases. However, the molecular mechanisms that contribute to atherosclerotic plaque rupture are incompletely characterized. We aimed to identify the genes related to atherosclerotic plaque progression that could serve as novel biomarkers and interventional targets for plaque progression. Methods:The datasets of GSE28829 in early vs. advanced atherosclerotic plaques and those of GSE41571 in stable vs. ruptured plaques from Gene Expression Omnibus (GEO) were analyzed by using bioinformatics methods. In addition, we used quantitative reverse transcription polymerase chain reaction (qRT-PCR) to verify the expression level of core genes in a mouse atherosclerosis model.Results: There were 29 common differentially expressed genes (DEGs) between the GSE28829 and GSE41571 datasets, and the DEGs were mainly enriched in the chemokine signaling pathway and the Staphylococcus aureus infection pathway (P<0.05). We identified 6 core genes (FPR3, CCL18, MS4A4A, CXCR4, CXCL2, and C1QB) in the protein-protein interaction (PPI) network, 3 of which (CXCR4, CXCL2, and CCL18) were markedly enriched in the chemokine signaling pathway. qRT-PCR analysis showed that the messenger RNA levels of two core genes (CXCR4 and CXCL2) increased significantly during plaque progression in the mouse atherosclerosis model. Conclusions:In summary, bioinformatics techniques proved useful for the screening and identification of novel biomarkers of disease. A total of 29 DEGs and 6 core genes were linked to atherosclerotic plaque progression, in particular the CXCR4 and CXCL2 genes.

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Section: Discussionmentioning

confidence: 99%

Identification of key pathways and core genes involved in atherosclerotic plaque progression

Yang

Yao

et al. 2021

Ann Transl Med

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“…1B, 1C). Commercially available CD71 mAb M-A712 has also been described before and was used to induce internalization of CD71 (6,24). However, cross-inhibition studies performed on Jurkat T cells revealed that mAb M-A712 recognizes a distinct CD71 epitope compared to VIP-1 or 5-528 (Supplemental Fig.…”

Section: Characterization Of the Cd71 Mabsmentioning

confidence: 99%

Iron Deprivation in Human T Cells Induces Nonproliferating Accessory Helper Cells

et al. 2020

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Iron uptake via the transferrin receptor (CD71) is a pivotal mechanism for T cell proliferation. Yet, it is incompletely understood if targeting of CD71 also affects the differentiation and functional polarization of primary human T cells. In this study, we demonstrate that inhibition of iron ingestion with blocking mAbs against CD71 induces nonproliferating T cells, which release high amounts of IL-2. Targeting of CD71 with blocking or nonblocking mAbs did not alter major signaling pathways and the activation of the transcription factors NF-kB, NFAT, or AP-1 as analyzed in Jurkat T cells. Growth arrest in iron-deficient (Fe-def) T cells was prevented upon addition of exogenous iron in the form of ferric ammonium citrate but was not reversible by exogenous IL-2. Surprisingly, protein synthesis was found to be intact in Fe-def T cells as demonstrated by comparable levels of CD69 upregulation and cytokine production with iron-sufficient T cells upon stimulation with CD3 plus CD28 mAbs. Indeed, high amounts of IL-2 were detectable in the supernatant of Fe-def T cells, which was accompanied with a reduced cell surface expression of IL-2R. When we used such Fedef T cells in allogeneic MLRs, we observed that these cells acquired an accessory cell function and stimulated the proliferation of bystander T cells by providing IL-2. Thus, the results of our study demonstrate that iron deprivation causes nonproliferating, altruistic T cells that can help and stimulate other immune cells by providing cytokines such as IL-2. ImmunoHorizons, 2020, 4: 165-177.

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“…To our knowledge, no direct comparison of the uptake and antiproliferative activity of Tf-bound and unbound V in mammalian cells have been reported . In this study, we used a well-established model cell line, A549 (human lung epithelial carcinoma), that highly expresses human transferrin receptor 1 (TfR1) , to clarify the role of Tf binding in the biological activities of V. The interactions of V(V/IV)–Tf adducts with TfR1 were also studied using a cell-free biolayer interferometry (BLI) model that was developed within our group. − …”

Section: Introductionmentioning

confidence: 99%

Vanadium(V/IV)–Transferrin Binding Disrupts the Transferrin Cycle and Reduces Vanadium Uptake and Antiproliferative Activity in Human Lung Cancer Cells

Levina

Lay

2020

Inorg. Chem.

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The role of vanadium binding to transferrin (Tf) in the biological activities of vanadium-based drugs is a matter of considerable debate. In order to determine whether V(V) and/or V(IV) binding to Tf (in apo, monoferric(III), and diferric(III) forms) enhances or inhibits biological activities, cellular V uptake and in vitro antiproliferative activity were examined in the presence and absence of different forms of Tf and other biomolecules under normoxic conditions. These data were combined with studies on V–Tf binding in cell culture medium and its role in Tf interactions with transferrin receptor 1 (TfR1), using the biolayer interferometry (BLI) model of the Tf cycle that was developed in our group. The results showed that both V(V) and V(IV) oxidation states efficiently bind to vacant Fe(III) binding sites of Tf even in the presence of a 20-fold molar excess of albumin, although V does not displace Tf-bound Fe(III) under these conditions. Binding of V(V) or V(IV) to Tf in cell culture medium drastically reduced its cellular uptake and antiproliferative activity in the A549 (human lung cancer) cell line that expresses TfR1. BLI and gel electrophoresis studies showed that V(V/IV) binding to partially Fe(III) saturated Tf did not enhance the affinity of Tf binding to TfR1 at pH 7.4 but did disrupt Tf conformational changes under endosome-mimicking conditions (pH 5.6, 0.10 mM citrate). Hence, it is postulated that the absence of a significant cellular uptake of Tf-bound V(V/IV) is likely to be due to the return of undissociated V(V/IV)–Tf adducts to the cell surface after the endosomal step. Collectively, these data show that the biotransformation of V-based drugs leads to V(V/IV)–Tf binding in the blood serum and inhibits, rather than enhances, the biological activity of such drugs under aerobic conditions. These results indicate that the design of V-based drugs that are stable enough to survive in the blood, enter cells intact, and release the active components intracellularly is likely to be required for their clinical success.

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Blocking transferrin receptor inhibits the growth of lung adenocarcinoma cells in vitro

Cited by 20 publications

References 43 publications

Identification of key pathways and core genes involved in atherosclerotic plaque progression

Identification of key pathways and core genes involved in atherosclerotic plaque progression

Iron Deprivation in Human T Cells Induces Nonproliferating Accessory Helper Cells

Vanadium(V/IV)–Transferrin Binding Disrupts the Transferrin Cycle and Reduces Vanadium Uptake and Antiproliferative Activity in Human Lung Cancer Cells

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