DNA damage triggers squamous metaplasia in human lung and mammary cells via mitotic checkpoints

Juan, Lucía San; Freije, Ana; Sanz-Gómez, Natalia; Jiménez-Matías, Beatriz; Pleguezuelos-Manzano, Cayetano; Sanz, Juan Ramón; Diego, Ernesto de; Naranjo, Sara; Gandarillas, Alberto

doi:10.1038/s41420-023-01330-3

Cited by 5 publications

(4 citation statements)

References 48 publications

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“…Interestingly, a previous study using human airway cells and a mouse model reported that TGF‐β induced airway squamous metaplasia via Smad signalling, which was blocked by an anti‐TGF‐β antibody [31]. The other study, using human lung and mammary cells, reported that DNA damage has the potential to drive squamous metaplasia via mitotic checkpoints [32]. Similar mechanisms may underlie salivary gland metaplasia.…”

Section: Discussionmentioning

confidence: 99%

TGF‐β3 from fibroblasts promotes necrotising sialometaplasia by suppressing salivary gland cell proliferation and inducing squamous metaplasia

Yoshimoto,

Yada,

Ishikawa

et al. 2024

The Journal of Pathology

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Necrotising sialometaplasia (NSM) is a non‐neoplastic lesion mainly arising in the minor salivary glands of the oral cavity. In the clinical features, NSM shows swelling with or without ulceration, and can mimic a malignant disease such as squamous cell carcinoma. Histopathologically, NSM usually shows the lobular architecture that is observed in the salivary glands. Additionally, acinar infarction and squamous metaplasia of salivary ducts and acini are observable. The aetiology of this lesion remains unknown, although it has a characteristic feature that sometimes requires clinical and histopathological differentiation from malignancy. In this study, we investigated upregulated genes in NSM compared with normal salivary glands, and focused on the TGF‐β3 (TGFB3) gene. The results of the histopathological studies clarified that fibroblasts surrounding the lesion express TGF‐β3. Moreover, in vitro studies using mouse salivary gland organoids revealed that TGF‐β3 suppressed salivary gland cell proliferation and induced squamous metaplasia. We demonstrated a possible aetiology of NSM by concluding that increased TGF‐β3 expression during wound healing or tissue regeneration played a critical role in cell proliferation and metaplasia. © 2024 The Pathological Society of Great Britain and Ireland.

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Section: Discussionmentioning

confidence: 99%

TGF‐β3 from fibroblasts promotes necrotising sialometaplasia by suppressing salivary gland cell proliferation and inducing squamous metaplasia

Yoshimoto,

Yada,

Ishikawa

et al. 2024

The Journal of Pathology

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“…Both chronic smoking and FBA have been shown to induce epithelium squamous metaplasia, it might be unclear if the cherry pit is only responsible factor, and smoking is additional factor contributed to the event. Juan et al showed that DNA damage has the potential to drive the squamous metaplasia via mitotic checkpoints, opening novel molecular candidate targets for lung squamous cell carcinoma ( 22 ). Furthermore, atypical adenomatous hyperplasia is prescribed as risk factor for lung cancer ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

Adenomatous hyperplasia induced by chronic cherry pit retention mimicking an endobronchial tumor-case series and systematic review of literature

Oruqaj,

Krombach,

Gattenloehner

et al. 2024

Front. Med.

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IntroductionEndobronchial foreign body aspiration is not common in adults, but it is a life-threatening event. Recurrent pneumonias by chronic retention of foreign body often lead to initial medical presentation of the patient. However, lymphoplasmacellular bronchitis with adenomatous hyperplasia and squamous epithelium metaplasia with complete or partial blockage of lobar bronchus mimicking lung tumor is rare in literature, and this particular condition is often misdiagnosed.Case presentationwe report our experience in the diagnostic and management of two elderly patients with recurrent pneumonia, admitted in hospital for further examination. In both patients, with no history of aspiration, the cherry pit was detected during bronchoscopy and recanalization with flexible cryoprobe, surrounded by purulent secretion, occluding completely the right upper lobe in the first case, and partially the left lower lobe associated with persistent actinomycosis in the second case, with signs of local inflammation, bronchial adenomatous hyperplasia mimicking lung tumor at initial bronchoscopic examination. Histology showed a lymphoplasmacellullar bronchitis with adenomatous hyperplasia and squamous epithelium metaplasia because of chronic retention of foreign body.ConclusionBronchoscopy examination should be considered in cases where there is an unresolved chronic cough with recurrent pneumonia or persistent actinomycosis in patients with high risk. Cryoprobe is a safe and feasible approach for treatment of airway obstructions due to chronic foreign body retention. Furthermore, relevant findings are discussed here, along with a review of the pathologic alterations and treatment modalities seen in chronic retention of foreign body and airway injury.

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“…We have proposed this DNA-induced differentiation response as an automatic mechanism that maintains the integrity of the tissue and at the same time, cleanses it of damaged precancerous cells. There is also evidence suggesting that the DDR pathways drive the epidermoid phenotype, even in the lung, thus controlling epithelial cell fate [ 16 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

DNA damage signalling histone H2AX is required for tumour growth

Contreras,

García-Gaipo,

Casar

et al. 2024

Cell Death Discov.

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Cancer most frequently develops in self-renewal tissues that are the target of genetic alterations due to mutagens or intrinsic DNA replication errors. Histone γH2AX has a critical role in the cellular DNA repair pathway cascade and contributes to genomic stability. However, the role of γH2AX in the ontology of cancer is unclear. We have investigated this issue in the epidermis, a self-renewal epithelium continuously exposed to genetic hazard and replication stress. Silencing H2AX caused cell cycle hyperactivation, impaired DNA repair and epidermal hyperplasia in the skin. However, mutagen-induced carcinogenesis was strikingly reduced in the absence of H2AX. KO tumours appeared significantly later than controls and were fewer, smaller and more benign. The stem cell marker Δp63 drastically diminished in the KO epidermis. We conclude that H2AX is required for tissue-making during both homoeostasis and tumourigenesis, possibly by contributing to the control and repair of stem cells. Therefore, although H2AX is thought to act as a tumour suppressor and our results show that it contributes to homeostasis, they also indicate that it is required for the development of cancer.

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DNA damage triggers squamous metaplasia in human lung and mammary cells via mitotic checkpoints

Cited by 5 publications

References 48 publications

TGF‐β3 from fibroblasts promotes necrotising sialometaplasia by suppressing salivary gland cell proliferation and inducing squamous metaplasia

TGF‐β3 from fibroblasts promotes necrotising sialometaplasia by suppressing salivary gland cell proliferation and inducing squamous metaplasia

Adenomatous hyperplasia induced by chronic cherry pit retention mimicking an endobronchial tumor-case series and systematic review of literature

DNA damage signalling histone H2AX is required for tumour growth

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