High levels of type VII collagen expression in recessive dystrophic epidermolysis bullosa cutaneous squamous cell carcinoma keratinocytes increases PI3K and MAPK signalling, cell migration and invasion

Pourreyron, Céline; Chen, M; McGrath, John A.; Salas‐Alanís, Julio C.; South, Andrew P.; Leigh, Irene M.

doi:10.1111/bjd.12715

Cited by 27 publications

(17 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Collagen synthesis and degradation affected by inflammation may contribute to changes in cell spreading and migration and, therefore, regeneration and disease progression. [84][85][86] Epithelial cell and epithelial stem cell/progenitor cell behavior in chronic inflammation is poorly characterized. The stem cell transcription factors array showed a significant decrease in the majority of LG epithelial stem/progenitor cell markers, such as Pax6, Sox6, Sox9, Six2, Klf4, and Notch2, that control LG development and regeneration.…”

Section: Discussionmentioning

confidence: 99%

Lacrimal Gland Inflammation Deregulates Extracellular Matrix Remodeling and Alters Molecular Signature of Epithelial Stem/Progenitor Cells

Umazume

Thomas

Campbell

et al. 2015

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PURPOSE. The adult lacrimal gland (LG) is highly regenerative and is able to repair itself even after substantial damage; however, this ability to regenerate is lost with the development of dry eye conditions in chronically inflamed LGs.This study compares changes in the cell adhesion and cell matrix molecules and stem cell transcription factors in the LGs of healthy mice and of two mouse models of Sjögren's syndrome: nonobese diabetic (NOD) and MRLlpr/lpr (MRL/lpr) mice during the early stage of inflammation. METHODS. TheLGs from 12-to 13-week-old female MRL/lpr and male NOD mice along with their respective control strains were harvested and divided into three pieces and processed for quantitative (q) RT-PCR and qRT-PCR Arrays, histology, immunohistochemistry, and Western blotting. RESULTS. The extracellular matrix (ECM) and adhesion molecules RT2 -PCR array combined with protein expression data revealed changes in the expression of integrins, matrix metalloproteinases, and other molecules, which are associated largely with invasion, attachment, and expansion of the lymphocytic cells, whereas changes in the stem cell transcription factors revealed substantial decrease in expression of transcription factors associated with epithelial stem/progenitor cell lineage. CONCLUSIONS.We concluded that the expression of several important ECM components is significantly deregulated in the LG of two murine models of Sjögren's syndrome, suggesting an alteration of the epithelial stem/progenitor cell niche. This may result in profound effects on localization, activation, proliferation, and differentiation of the LG stem/progenitor cells and, therefore, LG regeneration.

show abstract

Section: Discussionmentioning

confidence: 99%

Lacrimal Gland Inflammation Deregulates Extracellular Matrix Remodeling and Alters Molecular Signature of Epithelial Stem/Progenitor Cells

Umazume

Thomas

Campbell

et al. 2015

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…This disease is characterized by skin and mucosal fragility due to a decrease in Col7 formation (the main component of anchoring fibrils) which leads to blister formation and chronic skin traumatisms (risk factor for SCC) [71]. Considering the fact that patients with dominant dystrophic epidermolysis bullosa (1 normal COL7A1 allele which means 50% normal Col 7 formation) develop SCC less than RDEB patients [71], scientists are trying to increase Col7 formation through divers methods (gene, protein, and cell therapy), but it was observed that high levels of Col7 are correlated with an important activation of the phosphoinositide 3-kinase pathway that leads to an increased invasion in SCC keratinocytes; therefore this kind of therapies should be applied with caution [116]. Matrix metalloproteinases are molecules implicated in maintaining homeostasis of many tissues including skin, by proteolysis of extracellular matrix.…”

Section: Proteic and Other Potential Biomarkers Of Squamous Cell Cmentioning

confidence: 99%

From Normal Skin to Squamous Cell Carcinoma: A Quest for Novel Biomarkers

et al. 2016

View full text Add to dashboard Cite

Squamous cells carcinoma (SCC) is the second most frequent of the keratinocyte-derived malignancies after basal cell carcinoma and is associated with a significant psychosocial and economic burden for both the patient himself and society. Reported risk factors for the malignant transformation of keratinocytes and development of SCC include ultraviolet light exposure, followed by chronic scarring and inflammation, exposure to chemical compounds (arsenic, insecticides, and pesticides), and immune-suppression. Despite various available treatment methods and recent advances in noninvasive or minimal invasive diagnostic techniques, the risk recurrence and metastasis are far from being negligible, even in patients with negative histological margins and lymph nodes. Analyzing normal, dysplastic, and malignant keratinocyte proteome holds special promise for novel biomarker discovery in SCC that could be used in the future for early detection, risk assessment, tumor monitoring, and development of targeted therapeutic strategies.

show abstract

“…The aggressive nature of RDEB-SCC, including enhanced migration and invasion, has been confirmed by in vitro experiments using SCC cell lines with siRNA-induced COL7 depletion. 97 The cellular phenotype may vary depending on COL7 expression levels, 98 demonstrated when overexpression of COL7 in RDEB cells exceeds the physiological level of the protein. 98 Terminal differentiation of RDEB-SCC cells is suppressed in vivo and in xenograft models.…”

Section: Col7 In Wound Healing and Carcinogenesis Of Keratinocytesmentioning

confidence: 99%

“…97 The cellular phenotype may vary depending on COL7 expression levels, 98 demonstrated when overexpression of COL7 in RDEB cells exceeds the physiological level of the protein. 98 Terminal differentiation of RDEB-SCC cells is suppressed in vivo and in xenograft models. 97,99 In studies in which dermal components were also assessed, dermal tissue stiffening due to increased extracellular matrix production 57 and angiogenesis 99 have been shown to result from COL7 depletion in epidermal keratinocytes and to subsequently facilitate the development and aggressive nature of RDEB-SCC.…”

Section: Col7 In Wound Healing and Carcinogenesis Of Keratinocytesmentioning

confidence: 99%

Epidermal aspects of type VII collagen: Implications for dystrophic epidermolysis bullosa and epidermolysis bullosa acquisita

Watanabe

Natsuga

Shinkuma

et al. 2018

The Journal of Dermatology

View full text Add to dashboard Cite

Type VII collagen (COL7), a major component of anchoring fibrils in the epidermal basement membrane zone, has been characterized as a defective protein in dystrophic epidermolysis bullosa and as an autoantigen in epidermolysis bullosa acquisita. Although COL7 is produced and secreted by both epidermal keratinocytes and dermal fibroblasts, the role of COL7 with regard to the epidermis is rarely discussed. This review focuses on COL7 physiology and pathology as it pertains to epidermal keratinocytes. We summarize the current knowledge of COL7 production and trafficking, its involvement in keratinocyte dynamics, and epidermal carcinogenesis in COL7 deficiency and propose possible solutions to unsolved issues in this field.

show abstract

High levels of type VII collagen expression in recessive dystrophic epidermolysis bullosa cutaneous squamous cell carcinoma keratinocytes increases PI3K and MAPK signalling, cell migration and invasion

Abstract: Our data suggest caution when formulating strategies where delivery of type VII collagen is likely to exceed levels seen under normal physiological conditions in a patient group with a higher inherent risk of developing skin cancer.

Cited by 27 publications

References 36 publications

Lacrimal Gland Inflammation Deregulates Extracellular Matrix Remodeling and Alters Molecular Signature of Epithelial Stem/Progenitor Cells

Lacrimal Gland Inflammation Deregulates Extracellular Matrix Remodeling and Alters Molecular Signature of Epithelial Stem/Progenitor Cells

From Normal Skin to Squamous Cell Carcinoma: A Quest for Novel Biomarkers

Epidermal aspects of type VII collagen: Implications for dystrophic epidermolysis bullosa and epidermolysis bullosa acquisita

Contact Info

Product

Resources

About