Development of a Method for Producing oxLDL: Characterization of Their Effects on HPV-Positive Head and Neck Cancer Cells

Scalia, Alessandro; Kindt, Nadège; Trelcat, Anne; Nachtergael, Amandine; Duez, Pierre; Journé, Fabrice; Carlier, Stéphane

doi:10.3390/ijms232012552

Cited by 4 publications

(4 citation statements)

References 30 publications

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“…LOX-1 receptor and oxLDLs are associated with the development and progression of several pathologies, such as atherosclerosis, obesity, type 2 diabetes, and different cancers [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. Notably, in CaP, we have previously shown that LOX-1 activation by oxLDLs stimulates tumor angiogenesis [ 31 ], epithelial-mesenchymal transition, and tumorigenic potential, being determinant for tumor growth [ 32 ], which could explain why obese patients with CaP progress to more malignant stages in a shorter period of time compared to patients with average weight [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, the role of LOX-1 and oxLDLs is not only restricted to pathologies, such as atherosclerosis or endothelial dysfunction, but has also been associated with the progression of chronic pathologies, such as obesity [ 18 , 19 ], type II diabetes mellitus [ 20 , 21 ], and various types of cancer. The role of LOX-1 in cancer is related to the hallmarks of cancer, such as angiogenesis, invasion, metastasis, resisting cell death, and sustained proliferative signaling between others [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ], and has been addressed in depth in several reviews [ 20 , 33 , 34 , 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

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LOX-1 Activation by oxLDL Induces AR and AR-V7 Expression via NF-κB and STAT3 Signaling Pathways Reducing Enzalutamide Cytotoxic Effects

Duprat

Robles

Castillo

et al. 2023

IJMS

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The oxidized low-density lipoprotein receptor 1 (LOX-1) is one of the most important receptors for modified LDLs, such as oxidated (oxLDL) and acetylated (acLDL) low-density lipoprotein. LOX-1 and oxLDL are fundamental in atherosclerosis, where oxLDL/LOX1 promotes ROS generation and NF-κB activation inducing the expression of IL-6, a STAT3 activator. Furthermore, LOX-1/oxLDL function has been associated with other diseases, such as obesity, hypertension, and cancer. In prostate cancer (CaP), LOX-1 overexpression is associated with advanced stages, and its activation by oxLDL induces an epithelial-mesenchymal transition, increasing angiogenesis and proliferation. Interestingly, enzalutamide-resistant CaP cells increase the uptake of acLDL. Enzalutamide is an androgen receptor (AR) antagonist for castration-resistant prostate cancer (CRPC) treatment, and a high percentage of patients develop a resistance to this drug. The decreased cytotoxicity is promoted in part by STAT3 and NF-κB activation that induces the secretion of the pro-inflammatory program and the expression of AR and its splicing variant AR-V7. Here, we demonstrate for the first time that oxLDL/LOX-1 increases ROS levels and activates NF-κB, inducing IL-6 secretion and the activation of STAT3 in CRPC cells. Furthermore, oxLDL/LOX1 increases AR and AR-V7 expression and decreases enzalutamide cytotoxicity in CRPC. Thus, our investigation suggests that new factors associated with cardiovascular pathologies, such as LOX-1/oxLDL, may also promote important signaling axes for the progression of CRPC and its resistance to drugs used for its treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

LOX-1 Activation by oxLDL Induces AR and AR-V7 Expression via NF-κB and STAT3 Signaling Pathways Reducing Enzalutamide Cytotoxic Effects

Duprat

Robles

Castillo

et al. 2023

IJMS

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“…In order to investigate the influence of oxLDL on human umbilical vein endothelial cells (HUVECs) and on human leukaemia monocytic cell line (THP-1), we used our "homemade" oxLDL, where we isolated and oxidated LDL using our previously described protocol [27]. LDL and VLDL were first isolated from human plasma by serial precipitation and centrifugation steps.…”

Section: Oxldl Productionmentioning

confidence: 99%

“…LDL were separated from VLDL by high-performance liquid chromatography in an aqueous size-exclusion chromatography column. Then, LDL was oxidated by 5 µM CuSO 4 incubation while agarose gel electrophoresis was assessed to control the quality of the oxidation [27].…”

Section: Oxldl Productionmentioning

confidence: 99%

The Interplay between Atherosclerosis and Cancer: Breast Cancer Cells Increase the Expression of Endothelial Cell Adhesion Markers

Scalia,

Doumani,

Kindt

et al. 2023

Biology

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Cardiovascular diseases are the leading causes of death worldwide, closely followed by cancer. To investigate the impact of breast cancer cell lines (SKBR3, MCF-7, and MDA-MB-231) on endothelial cell adhesion, a blended medium containing 30% breast-cancer-conditioned medium was prepared. This medium was then exposed to human umbilical vein endothelial cells (HUVECs) and monocytes (THP-1) for 48 h. Homemade oxidized low-density lipoproteins (oxLDL) were optionally added to the blended medium. Immunofluorescence was performed to assess the expression of E-selectin, connexin-43, and ICAM-1 on HUVECs, as well as LOX-1, CD36, and CD162 on THP-1. Additionally, unoxidized LDL was exposed to the three breast cancer cell lines for 48 h, and the formation of oxLDL was quantified. Our results revealed an upregulation of all six adhesion markers involved in the initiation of atherosclerosis when HUVECs and THP-1 were exposed to the breast-cancer-conditioned medium. Furthermore, this expression was further increased by exposure to oxLDL. We also observed a significant elevation in oxLDL levels when LDL was exposed to breast cancer cells. In conclusion, our findings successfully demonstrate an increased LDL oxidation in the presence of breast cancer cells, accompanied by an augmented expression of receptors involved in atherosclerosis initiation. These findings shed new light on the clinically observed interplay between atherosclerosis and cancer.

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Ligand-dependent CD36 functions in cancer progression, metastasis, immune response, and drug resistance

Xia,

Zhou,

Chen

et al. 2023

Biomedicine & Pharmacotherapy

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Development of a Method for Producing oxLDL: Characterization of Their Effects on HPV-Positive Head and Neck Cancer Cells

Cited by 4 publications

References 30 publications

LOX-1 Activation by oxLDL Induces AR and AR-V7 Expression via NF-κB and STAT3 Signaling Pathways Reducing Enzalutamide Cytotoxic Effects

LOX-1 Activation by oxLDL Induces AR and AR-V7 Expression via NF-κB and STAT3 Signaling Pathways Reducing Enzalutamide Cytotoxic Effects

The Interplay between Atherosclerosis and Cancer: Breast Cancer Cells Increase the Expression of Endothelial Cell Adhesion Markers

Ligand-dependent CD36 functions in cancer progression, metastasis, immune response, and drug resistance

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