NTCU induced pre-malignant and malignant stages of lung squamous cell carcinoma in mice model

Zakaria, Muhammad Asyaari; Rajab, Nor Fadilah; Chua, Eng Wee; Selvarajah, Gayathri Thevi; Masre, Siti Fathiah

doi:10.1038/s41598-021-01988-8

Cited by 4 publications

(6 citation statements)

References 38 publications

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“…In comparison, a few mouse SCC models were validated for use in preclinical cancer chemoprevention studies. We have developed a mouse SCC model induced by carcinogen N-nitroso-trischloroethylurea (NTCU) that has similar histopathological features and keratin staining to human lung SCC ( 5 ), and been widely used worldwide in chemoprevention, carcinogenesis, and imaging studies ( 6 , 7 ). In the current study, we evaluated the chemopreventive efficacy in these two carcinogen-induced primary lung tumor models that represent the major subtypes of lung cancer.…”

Section: Introductionmentioning

confidence: 99%

Aerosolized miR-138-5p and miR-200c targets PD-L1 for lung cancer prevention

et al. 2023

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The development of chemopreventive strategies with the ability to prevent the progression of lung lesions to malignant cancers would reduce the mortality and morbidity resulting from this deadly disease. Delivery of microRNA (miRNA) by inhalation is a novel method for lung cancer prevention. In this study, we investigated the combined efficacy of aerosolized miR-138-5p and miR-200c miRNA mimics in lung cancer prevention. Combination of the two miRNAs inhibited Benzo(a)pyrene (B((a))P)-induced lung adenomas and N-nitroso-tris-chloroethylurea (NTCU)-induced lung squamous cell carcinomas with no detectable side effects. Using single-cell RNA sequencing (scRNA-seq) and imaging mass cytometry (IMC), we found that both miRNAs inhibited programmed cell death ligand 1 (PD-L1) expression. Our flow cytometry results showed that aerosolized delivery of combined miRNAs increased CD4+ and CD8+ T cells and reduced the expression of programmed cell death protein 1 (PD-1) and T-regulatory cells. Our results demonstrated that the delivery of aerosolized microRNAs targeting PD-L1 can be highly effective in preventing lung cancer development and progression in mice.

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Section: Introductionmentioning

confidence: 99%

Aerosolized miR-138-5p and miR-200c targets PD-L1 for lung cancer prevention

et al. 2023

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“…Then, the lungs were immediately harvested for hematoxylin and eosin (H&E) staining, picrosirius red (PSR) staining, quantitative real-time polymerase chain reaction (RT-qPCR), and immunohistochemistry staining (IHC). The development of pre-malignant lung SCC in vivo in this study was conducted following our previously published work [ 27 ]. In our previous work and in this study, we gave 0.04 M NTCU treatment for 15 weeks to induce pre-malignant lung SCC.…”

Section: Methodsmentioning

confidence: 99%

Rigid Tissue Increases Cytoplasmic pYAP Expression in Pre-Malignant Stage of Lung Squamous Cell Carcinoma (SCC) In Vivo

Zakaria

Kiew

Rajab

et al. 2022

CIMB

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Increased tissue rigidity is able to activate the Hippo signaling pathway, leading to YAP inactivation by phosphorylation and translocation into the cytoplasm. Accumulating evidence suggests that cytoplasmic pYAP serves as a tumor suppressor and could be a prognostic biomarker for several solid cancers. However, the relationship between tissue rigidity and cytoplasmic pYAP expression in the early stage of lung squamous cell carcinoma (SCC) remains elusive; this was determined in this study by using a mouse model. Female BALB/c mice were assigned into two groups (n = 6; the vehicle (VC) and the pre-malignant (PM) group, which received 70% acetone and 0.04 M N-nitroso-tris-chloroethylurea (NTCU) for 15 weeks, respectively. In this study, the formation of hyperplasia and metaplasia lesions was found in the PM group, indicating the pre-malignant stage of lung SCC. The pre-malignant tissue appeared to be more rigid as characterized by significantly higher (p < 0.05) epithelium thickness, proliferative activity, and collagen content than the VC group. The PM group also had a significantly higher (p < 0.05) cytoplasmic pYAP protein expression than the VC group. In conclusion, increased tissue rigidity may contribute to the upregulation of cytoplasmic pYAP expression, which may act as a tumor suppressor in the early stage of lung SCC.

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“…Animal experiments were reviewed and approved by Universiti Kebangsaan Malaysia Animal Ethics Committee (FSK/2017/FATHIAH/24-MAY/846-MAY-2017-MAY-2020) and conducted in compliance with the ARRIVE guidelines. All procedures involving lung SCC animal model development were performed in our previous published work [ 28 ]. Briefly, lung SCC was established in female BALB/c mice using N-nitroso-tris-chloroethylurea (NTCU).…”

Section: Methodsmentioning

confidence: 99%

“…In the negative control group, the tissues were incubated with 10% NGS only, without an anti-TNC primary antibody. After that, the IHC reactions on tissues were developed using the 3,3′-Diaminobenzidine (DAB) (Dako, Glostrup, Denmark) and counterstained with hematoxylin [ 28 , 40 ]. Finally, the tissues were dehydrated with alcohol and xylene before being mounted with DPX.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, we aim to evaluate the tissue rigidity by analyzing the collagen (content, diameter, and rigidity) and tenascin C expression in NTCU-induced lung SCC tissues in mice models. This model was suggested as one of the best chemically-induced models that can closely mimic human lung SCC [ 28 , 29 , 30 ]. Collagen was chosen as it is the main component of ECM in cancer tissues.…”

Section: Introductionmentioning

confidence: 99%

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Tissue Rigidity Increased during Carcinogenesis of NTCU-Induced Lung Squamous Cell Carcinoma In Vivo

et al. 2022

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Increased tissue rigidity is an emerging hallmark of cancer as it plays a critical role in promoting cancer growth. However, the field lacks a defined characterization of tissue rigidity in dual-stage carcinogenesis of lung squamous cell carcinoma (SCC) in vivo. Pre-malignant and malignant lung SCC was developed in BALB/c mice using N-nitroso-tris-chloroethylurea (NTCU). Picro sirius red staining and atomic force microscopy were performed to measure collagen content and collagen (diameter and rigidity), respectively. Then, the expression of tenascin C (TNC) protein was determined using immunohistochemistry staining. Briefly, all tissue rigidity parameters were found to be increased in the Cancer group as compared with the Vehicle group. Importantly, collagen content (33.63 ± 2.39%) and TNC expression (7.97 ± 2.04%) were found to be significantly higher (p < 0.05) in the Malignant Cancer group, as compared with the collagen content (18.08 ± 1.75%) and TNC expression (0.45 ± 0.53%) in the Pre-malignant Cancer group, indicating increased tissue rigidity during carcinogenesis of lung SCC. Overall, tissue rigidity of lung SCC was suggested to be increased during carcinogenesis as indicated by the overexpression of collagen and TNC protein, which may warrant further research as novel therapeutic targets to treat lung SCC effectively.

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NTCU induced pre-malignant and malignant stages of lung squamous cell carcinoma in mice model

Cited by 4 publications

References 38 publications

Aerosolized miR-138-5p and miR-200c targets PD-L1 for lung cancer prevention

Aerosolized miR-138-5p and miR-200c targets PD-L1 for lung cancer prevention

Rigid Tissue Increases Cytoplasmic pYAP Expression in Pre-Malignant Stage of Lung Squamous Cell Carcinoma (SCC) In Vivo

Tissue Rigidity Increased during Carcinogenesis of NTCU-Induced Lung Squamous Cell Carcinoma In Vivo

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