Irradiated fibroblasts increase interleukin-6 expression and induce migration of head and neck squamous cell carcinoma

Suzuki, Shinsuke; Toyoma, Satoshi; Kawasaki, Yohei; Yamada, Tetsuji

doi:10.1371/journal.pone.0262549

Cited by 10 publications

(5 citation statements)

References 32 publications

(44 reference statements)

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“…Surprisingly, despite 15 out of the 36 cytokines investigated being detectable in the chip effluent, no significant changes in cytokine release were observed following irradiation with 5 × 2 Gy. This contrasts with studies on HNSCC cell lines, which found that irradiation (2, 5 and 10 Gy) stimulated the release of IL6 within 24 h post-irradiation from fibroblasts, which will be present in the tumour biopsy samples, as well as reducing the survival of HNSCC cells [62]. Suzuki et al [62] also found that the migration of HNSCC cells induced by irradiated fibroblasts was mediated by IL6, although this may simply represent the differences between the 2D cell line culture and the 3D tissue where the number of fibroblasts will be lower.…”

Section: Discussioncontrasting

confidence: 76%

“…This contrasts with studies on HNSCC cell lines, which found that irradiation (2, 5 and 10 Gy) stimulated the release of IL6 within 24 h post-irradiation from fibroblasts, which will be present in the tumour biopsy samples, as well as reducing the survival of HNSCC cells [62]. Suzuki et al [62] also found that the migration of HNSCC cells induced by irradiated fibroblasts was mediated by IL6, although this may simply represent the differences between the 2D cell line culture and the 3D tissue where the number of fibroblasts will be lower. The secretion of cytokines into the effluent over the incubation time on the perfusion device further supports the maintenance of the functionality of the tissue ex vivo.…”

Section: Discussioncontrasting

confidence: 76%

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Head and Neck Squamous Cell Carcinoma Biopsies Maintained Ex Vivo on a Perfusion Device Show Gene Changes with Time and Clinically Relevant Doses of Irradiation

Green,

Baldwin,

England

et al. 2023

Cancers

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Advancements in 3-Dimensional (3D) culture models for studying disease have increased significantly over the last two decades, but fully understanding how these models represent in vivo still requires further investigation. The current study investigated differences in gene expression between a baseline sample and that maintained on a tissue-on-chip perfusion device for up to 96 h, with and without clinically-relevant doses of irradiation, to allow differentiation of model and treatment effects. Tumour tissue samples from 7 Head and Neck Squamous Cell Carcinomas (HNSCC) patients were sub-divided and either fixed immediately upon excision or maintained in a tissue-on-chip device for 48 and 96 h, with or without 2 Gray (Gy) or 10 Gy irradiation. Gene expression was measured using an nCounter® PanCancer Progression Panel. Differentially expressed genes between pre- and post-ex vivo culture, and control and irradiated samples were identified using nSolver software (version 4.0). The secretome from the tumour-on-chip was analysed for the presence of cytokines using a Proteome Profiler™ platform. Significant numbers of genes both increased (n = 6 and 64) and decreased (n = 18 and 58) in expression in the tissue maintained on-chip for 48 and 96 h, respectively, compared to fresh tissue; however, the irradiation schedule chosen did not induce significant changes in gene expression or cytokine secretion. Although HNSCC tissue maintained ex vivo shows a decrease in a large proportion of altered genes, 25% and 53% (48 and 96 h) do show increased expression, suggesting that the tissue remains functional. Irradiation of tumour tissue-on-chip needs to be conducted for longer time periods for specific gene changes to be observed, but we have shown, for the first time, the feasibility of using this perfusion platform for studying the genomic response of HNSCC tissue biopsies.

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Section: Discussioncontrasting

confidence: 76%

Section: Discussioncontrasting

confidence: 76%

Head and Neck Squamous Cell Carcinoma Biopsies Maintained Ex Vivo on a Perfusion Device Show Gene Changes with Time and Clinically Relevant Doses of Irradiation

Green,

Baldwin,

England

et al. 2023

Cancers

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“…It might be possible that due to the time distance from the injury, parts of the produced IL-6 had already been degraded. According to other studies, irradiation can increase or decrease IL-6 expression; so, in general, it seems that irradiation influences the gene expression of IL-6 just slightly [47,48].…”

Section: Discussionmentioning

confidence: 87%

The Influence of Different Irradiation Regimens on Inflammation and Vascularization in a Random-Pattern Flap Model

Müller-Seubert,

Ostermaier,

Horch

et al. 2023

JPM

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Background: Irradiation plays an important role in the oncological treatment of various tumor entities. The aim of the study was to investigate the influence of different irradiation regimens on random-pattern flaps at the molecular and histopathological levels. Methods: Twenty-five rats underwent harvesting of bilateral random-pattern fasciocutaneous flaps. The right flaps received irradiation, while the left flaps served as non-irradiated intraindividual controls. Five rats served as a non-irradiated control group. Four different irradiation regimens with give rats each were tested: 20 Gy postoperatively, 3 × 12 Gy postoperatively, 20 Gy preoperatively, and 3 × 12 Gy preoperatively. Two weeks after surgery, HE staining and immunohistochemical staining for CD68 and ERG, as well as PCR analysis to detect Interleukin 6, HIF-1α, and VEGF, were performed. Results: A postoperative cumulative higher dose of irradiation appeared to result in an increase in necrosis, especially in the superficial layers of the flap compared to preoperative or single-stage irradiation. In addition, we observed increased expression of VEGF and HIF-1α in all irradiation groups. Conclusion: Even though no statistically significant differences were found between the different groups, there was a tendency for fractional postoperative irradiation with a higher total dose to have a more harmful effect compared to preoperative or single-dose irradiation.

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“…Suzuki et al showed faster migration of HNSCC cells (SAS and FaDu cell lines) in co-cultures with fibroblasts, especially after their irradiation. They also confirmed that the migration of HNSCC cells was induced by fibroblast-secreted IL-6 [ 22 ]. However, unlike our methodology, the Suzuki group performed a migration assay with a mechanical barrier between HNSCCs and fibroblasts.…”

Section: Discussionmentioning

confidence: 67%

The Effect of Radiotherapy on Cell Survival and Inflammatory Cytokine and Chemokine Secretion in a Co-Culture Model of Head and Neck Squamous Cell Carcinoma and Normal Cells

et al. 2023

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Radiotherapy (RT) is one of the main treatments for head and neck squamous cell carcinomas (HNSCCs). Unfortunately, radioresistance is observed in many cases of HNSCCs. The effectiveness of RT depends on both the direct effect inducing cell death and the indirect effect of changing the tumor microenvironment (TME). Knowledge of interactions between TME components after RT may help to design a new combined treatment with RT. In the study, we investigated the effect of RT on cell survival and cell secretion in a co-culture model of HNSCCs in vitro. We examined changes in cell proliferation, colony formation, cell cycle phases, type of cell death, cell migration and secretion after irradiation. The obtained results suggest that the presence of fibroblasts and endothelial cells in co-culture with HNSCCs inhibits the function of cell cycle checkpoints G1/S and G2/M and allows cells to enter the next phase of the cell cycle. We showed an anti-apoptotic effect in co-culture of HNSCCs with fibroblasts or endothelial cells in relation to the execution phase of apoptosis, although we initially observed increased activation of the early phase of apoptosis in the co-cultures after irradiation. We hypothesize that the anti-apoptotic effect depends on increased secretion of IL-6 and MCP-1.

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Irradiated fibroblasts increase interleukin-6 expression and induce migration of head and neck squamous cell carcinoma

Cited by 10 publications

References 32 publications

Head and Neck Squamous Cell Carcinoma Biopsies Maintained Ex Vivo on a Perfusion Device Show Gene Changes with Time and Clinically Relevant Doses of Irradiation

Head and Neck Squamous Cell Carcinoma Biopsies Maintained Ex Vivo on a Perfusion Device Show Gene Changes with Time and Clinically Relevant Doses of Irradiation

The Influence of Different Irradiation Regimens on Inflammation and Vascularization in a Random-Pattern Flap Model

The Effect of Radiotherapy on Cell Survival and Inflammatory Cytokine and Chemokine Secretion in a Co-Culture Model of Head and Neck Squamous Cell Carcinoma and Normal Cells

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