Mouse tail skin wholemount staining and intravital calcium imaging

Xie, Yuhua; Chen, Ting

doi:10.1016/j.xpro.2022.101235

Cited by 3 publications

(1 citation statement)

References 12 publications

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“…Lastly, we opted to administer DMBA/TPA treatments to the tail skin of mice to avoid shaving the dorsal skin with every treatment which would irritate or damage the epidermis and potentially affect results interpretation. Furthermore, murine tail skin is more similar to human thin skin since it contains less hair follicles and has a thicker epidermis than that of mouse dorsal skin, making it a more suitable selection to model human cSCC carcinogenesis (Xie & Chen, 2022).…”

Section: Discussionmentioning

confidence: 99%

Pannexin 1 and Pannexin 3 differentially regulate the tumorigenic properties of cutaneous squamous cell carcinoma

O’Donnell,

Johnston,

Bhatt

et al. 2024

Preprint

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Pannexin (PANX) channels are present in skin and facilitate the movement of signalling molecules during cellular communication. PANX1 and PANX3 function in skin homeostasis and keratinocyte differentiation but were previously reduced in a small cohort of human cutaneous squamous cell carcinoma (cSCC) tumours compared to normal epidermis. In our study, we used SCC-13 cells, limited publicly available RNA-seq data and a larger cohort of cSCC patient-matched samples to analyze PANX1 and PANX3 expression and determine the association between their dysregulation and the malignant properties of cSCC. In a bioinformatics analysis,PANX1transcripts were increased in both cSCC and head and neck SCC tumours compared to normal tissues, butPANX3mRNA showed no differences. However, in our own patient cohort,PANX3transcripts were decreased in cSCC tissue compared to patient-matched aged skin, whereas PANX1 was upregulated in cSCC. PANX1 localized to all cell types within the cSCC tumour microenvironment and increased levels were associated with larger tumour dimensions. To investigate PANX1 channel function, we treated SCC-13 cells with PANX1 inhibitors which markedly reduced cell growth and migration. To assess PANX3 function in cutaneous carcinogenesis, we employed the DMBA/TPA carcinoma model using our globalPanx3knockout (KO) mice, where 60% of wildtype and 100% of KO mice formed pre-cancerous papillomas. Average papilloma volumes at endpoint were significantly increased in KO mice and showed moderate evidence of increases in KO mice over time. Collectively, these findings suggest PANX1 and PANX3 dysregulation may have potential tumour promoting and suppressive effects for keratinocyte transformation, respectively.Key points summaryPannexin 1 and pannexin 3 are channel-forming proteins which are critical in the normal maintenance and function of keratinocytes in the skin but may become altered in cutaneous squamous cell carcinoma (cSCC) tumours.In this study, using a combination of culture models, mouse models and patient-derived tissues, we found pannexin 1 levels are increased in cSCC tumours and present in all tumour cell types, functioning to increase cSCC cell growth and migration.On the other hand, pannexin 3 levels are decreased in cSCC tumours and this protein reduces the incidence and growth of pre-cancerous lesions.Taken together, our data indicates that in cSCC these pannexin family members seem to have opposite effects, where pannexin 1 is pro-tumorigenic and pannexin 3 is anti-tumorigenic.These results help us to better understand the mechanisms of malignant transformation of keratinocytes and offer a new potential therapeutic target for the treatment of advanced cSCC.

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Section: Discussionmentioning

confidence: 99%

Pannexin 1 and Pannexin 3 differentially regulate the tumorigenic properties of cutaneous squamous cell carcinoma

O’Donnell,

Johnston,

Bhatt

et al. 2024

Preprint

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Pannexin 1 and pannexin 3 differentially regulate the cancer cell properties of cutaneous squamous cell carcinoma

O'Donnell,

Johnston,

Bhatt

et al. 2024

The Journal of Physiology

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Pannexin (PANX) channels are present in skin and facilitate the movement of signalling molecules during cellular communication. PANX1 and PANX3 function in skin homeostasis and keratinocyte differentiation but were previously reduced in a small cohort of human cutaneous squamous cell carcinoma (cSCC) tumours compared to normal epidermis. In our study we used SCC‐13 cells, limited publicly available RNA‐seq data and a larger cohort of cSCC patient‐matched samples to analyse PANX1 and PANX3 expression and determine the association between their dysregulation and the malignant properties of cSCC. In a bioinformatics analysis, PANX1 transcripts were increased in cSCC and head and neck SCC tumours compared to normal tissues, but PANX3 mRNA showed no differences. However, in our own cohort PANX3 transcripts were decreased in cSCC compared to patient‐matched aged skin, whereas PANX1 protein was upregulated in cSCC. PANX1 localized to all regions within the cSCC tumour microenvironment, and increased levels were associated with larger tumour dimensions. To investigate PANX1 function in SCC‐13 cells, we deleted PANX1 via CRISPR/Cas9 and treated with PANX1 inhibitors, which markedly reduced cell growth and migration. To assess PANX3 function in cutaneous carcinogenesis, we employed the 7,12‐dimethylbenz(a)anthracene/12‐otetradecanoylphorbol‐13‐acetate (DMBA/TPA) model using our global Panx3 knockout (KO) mice, where 60% of wild‐type and 100% of KO mice formed precancerous papillomas. Average papilloma volumes at endpoint were significantly increased in KO mice and showed moderate evidence of increases in KO mice over time. Collectively, these findings suggest PANX1 and PANX3 dysregulation may have potential tumour‐promoting and tumour‐suppressive effects for keratinocyte transformation, respectively. imageKey points Pannexin 1 (PANX1) and pannexin 3 (PANX3) are channel‐forming proteins which are critical in the normal maintenance and function of keratinocytes in the skin but may become altered in cutaneous squamous cell carcinoma (cSCC) tumours. In this study we used a combination of culture models, mouse models and patient‐derived tissues. We found PANX1 levels are increased in cSCC tumours and present in all tumour regions, functioning to promote cSCC cell growth and migration. Conversely, PANX3 levels are decreased in cSCC tumours, and this protein reduces the incidence and growth of precancerous lesions. Taken together our data indicate that in cSCC these pannexin family members seem to have opposite effects, in either promoting or restricting cancer cell properties. These results help us to better understand the mechanisms of malignant transformation of keratinocytes and offer a new potential therapeutic target for the treatment of advanced cSCC.

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Ultrasound Irradiation as a Candidate Procedure to Improve the Transdermal Drug Delivery to the Tail Edema of a Mouse Model

Kumegawa,

Suzuki,

Fujimoto

et al. 2024

IJMS

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Drug therapy for secondary lymphedema has not yet been established. Conventional oral and intravenous administration is difficult to administer in sufficient doses due to adverse events. Therefore, it is necessary to develop a transdermal delivery system that can deliver high concentrations of drugs to the edema area. In this study, we examined the efficacy of transdermal drug delivery in a mouse model of tail edema using ultrasound irradiation (sonication method). Ultrasound irradiation can deliver high-molecular-weight substances subcutaneously, and the percutaneous administration of clobetasol propionate to the mouse tail edema model prevented the enlargement of lymphatic vessels with reduced tail volume. Therefore, steroid administration utilizing ultrasound irradiation is effective in decreasing tail swelling in a mouse tail edema model. Thus, ultrasound irradiation could have the potential to innovate the treatment of secondary lymphedema by directly administering the drug to the edema.

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Mouse tail skin wholemount staining and intravital calcium imaging

Cited by 3 publications

References 12 publications

Pannexin 1 and Pannexin 3 differentially regulate the tumorigenic properties of cutaneous squamous cell carcinoma

Pannexin 1 and Pannexin 3 differentially regulate the tumorigenic properties of cutaneous squamous cell carcinoma

Pannexin 1 and pannexin 3 differentially regulate the cancer cell properties of cutaneous squamous cell carcinoma

Ultrasound Irradiation as a Candidate Procedure to Improve the Transdermal Drug Delivery to the Tail Edema of a Mouse Model

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