Transcutaneous carbon dioxide application suppresses the expression of cancer-associated fibroblasts markers in oral squamous cell carcinoma xenograft mouse model

Tadokoro, Yoshiaki; Takeda, Daisuke; Murakami, Aki; Yatagai, Nanae; Saito, Izumi; Arimoto, Satomi; Kakei, Yasumasa; Akashi, Masaya; Hasegawa, Takumi

doi:10.1371/journal.pone.0290357

Cited by 3 publications

(1 citation statement)

References 46 publications

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“…More importantly, these surface markers are not specific. For instance, PDPN is found on lymphatic endothelial cells, αSMA is expressed by pericellular cells, and FAP is present on bone mesenchymal cells (48). Therefore, CAFs and different subgroups are not defined according to certain molecular characteristics alone.…”

Section: Discussionmentioning

confidence: 99%

BNIP3 + cancer-associated fibroblasts and their associated genes are accelerators of pancreatic cancer

Shao,

Zhang,

Zhao

et al. 2024

Preprint

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Background Pancreatic cancer is one of the most malignant gastrointestinal tumors. Due to the difficulty of early diagnosis and limited treatment, the prognosis of pancreatic cancer patients is very poor. Pancreatic cancer is characterized by high interstitial fibrosis, in which activation of cancer-associated fibroblasts (CAFs) plays a key role. CAFs is the most abundant cell in the pancreatic tumor microenvironment, with a high degree of plasticity, and participates in various processes of tumor development through crosstalk with tumor cells and other cells in the microenvironment. Elucidate the heterogeneity of CAFs and its mechanism of action, which helps find a new effective treatment for pancreatic cancer. Methods We used single-cell RNA sequencing (scRNA-seq) transcriptomics to analyze fibroblasts from pancreatic cancer patient specimens. This approach was able to identify key subpopulations of fibroblasts and elucidate their contribution to pancreatic cancer progression. Subsequently, we established a prediction model for pancreatic cancer using Cox regression and the LASSO algorithm and conducted cell experiments to verify it. Results Our study identified a BNIP3 + tumor-associated fibroblast and used this cell-associated gene to construct a prognostic model of pancreatic cancer, a feature that effectively divided PDAC patients into high-risk and low-risk groups and outperformed traditional clinicopathological features in predicting survival outcomes in pancreatic cancer patients. In vitro co-culture experiments showed that BNIP3 + fibroblasts could have more effects on pancreatic cancer cells. Conclusion We screened C1 BNIP3 + pancreatic cancer-associated fibroblasts, which advanced our knowledge and understanding of CAFs heterogeneity. The prognostic model we constructed can effectively predict the prognosis and treatment response of pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

BNIP3 + cancer-associated fibroblasts and their associated genes are accelerators of pancreatic cancer

Shao,

Zhang,

Zhao

et al. 2024

Preprint

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Correction: Transcutaneous carbon dioxide application suppresses the expression of cancer-associated fibroblasts markers in oral squamous cell carcinoma xenograft mouse model

2024

PLoS ONE

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Exposure of Primary Human Skin Fibroblasts to Carbon Dioxide-Containing Solution Significantly Reduces TGF-β-Induced Myofibroblast Differentiation In Vitro

Fleckner,

Döhmen,

Salz

et al. 2024

IJMS

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Wound healing as a result of a skin injury involves a series of dynamic physiological processes, leading to wound closure, re-epithelialization, and the remodeling of the extracellular matrix (ECM). The primary scar formed by the new ECM never fully regains the original tissue’s strength or flexibility. Moreover, in some cases, due to dysregulated fibroblast activity, proliferation, and differentiation, the normal scarring can be replaced by pathological fibrotic tissue, leading to hypertrophic scars or keloids. These disorders can cause significant physical impairment and psychological stress and represent significant challenges in medical management in the wound-healing process. The present study aimed to investigate the therapeutic effects of exogenously applied carbon dioxide (CO2) on fibroblast behavior, focusing on viability, proliferation, migration, and differentiation to myofibroblasts. We found that CO2 exposure for up to 60 min did not significantly affect fibroblast viability, apoptosis rate, or proliferation and migration capacities. However, a notable finding was the significant reduction in α-smooth muscle actin (α-SMA) protein expression, indicative of myofibroblast differentiation inhibition, following CO2 exposure. This effect was specific to CO2 and concentration as well as time-dependent, with longer exposure durations leading to greater reductions in α-SMA expression. Furthermore, the inhibition of myofibroblast differentiation correlated with a statistically significantly reduced glycolytic and mitochondrial energy metabolism, and as a result, with a reduced ATP synthesis rate. This very noticeable decrease in cellular energy levels seemed to be specific to CO2 exposure and could not be observed in the control cultures using nitrogen (N2)-saturated solutions, indicating a unique and hypoxia-independent effect of CO2 on fibroblast metabolism. These findings suggest that exogenously applied CO2 may possess fibroblast differentiation-reducing properties by modulating fibroblast’s energy metabolism and could offer new therapeutic options in the prevention of scar and keloid development.

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Transcutaneous carbon dioxide application suppresses the expression of cancer-associated fibroblasts markers in oral squamous cell carcinoma xenograft mouse model

Cited by 3 publications

References 46 publications

BNIP3 + cancer-associated fibroblasts and their associated genes are accelerators of pancreatic cancer

BNIP3 + cancer-associated fibroblasts and their associated genes are accelerators of pancreatic cancer

Correction: Transcutaneous carbon dioxide application suppresses the expression of cancer-associated fibroblasts markers in oral squamous cell carcinoma xenograft mouse model

Exposure of Primary Human Skin Fibroblasts to Carbon Dioxide-Containing Solution Significantly Reduces TGF-β-Induced Myofibroblast Differentiation In Vitro

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