Extracellular Vesicles as Biomarkers for the Detection of a Tumor Marker Gene in Epidermolysis Bullosa-Associated Squamous Cell Carcinoma

Sun, Yuchen; Woess, Katharina; Kienzl, Melanie; Reichl, Victoria; Feinle, Andrea; Wimmer, Monika; Zauner, Roland; Wally, Verena; Luetz-Meindl, Ursula; Mellerio, Jemima E.; Fuentes, Ignacia; South, Andrew P.; Bauer, Johann; Reichelt, Julia; Furihata, Tomomi; Guttmann‐Gruber, Christina; Hofbauer, Josefina Piñón

doi:10.1016/j.jid.2017.11.022

Cited by 16 publications

(18 citation statements)

References 13 publications

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“…Collagen VII (COL7) deficiency in recessive dystrophic epidermolysis bullosa (RDEB) skin and extracutaneous tissues favors squamous cell carcinoma (SCC) development. The figure summarizes literature findings on relevant pro-tumorigenic processes triggered by COL7 loss in RDEB keratinocytes, fibroblasts and lymphoid organs [42,44,49,52,57,58,59,61,62,63,64,67,84]. Red up arrows indicate increase/up-regulation, green down arrows indicate decrease/down-regulation.…”

Section: Dystrophic Ebmentioning

confidence: 95%

“…Recently Ct-OATPB1B3 mRNA has been found in extracellular-vesicles (EVs) released in the culture medium by RDEB-SCC cells and in the bloodstream of tumor-bearing immunodeficient mice upon injection with human RDEB-SCC cells. These findings draw attention to the role of SCC-derived EVs and their molecular cargo in RDEB-SCC pathogenesis, and to their potential usage as diagnostic and prognostic factors of the disease [63].…”

Section: Dystrophic Ebmentioning

confidence: 99%

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Epidermolysis Bullosa-Associated Squamous Cell Carcinoma: From Pathogenesis to Therapeutic Perspectives

Condorelli

Dellambra

Logli

et al. 2019

IJMS

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Epidermolysis bullosa (EB) is a heterogeneous group of inherited skin disorders determined by mutations in genes encoding for structural components of the cutaneous basement membrane zone. Disease hallmarks are skin fragility and unremitting blistering. The most disabling EB (sub)types show defective wound healing, fibrosis and inflammation at lesional skin. These features expose patients to serious disease complications, including the development of cutaneous squamous cell carcinomas (SCCs). Almost all subjects affected with the severe recessive dystrophic EB (RDEB) subtype suffer from early and extremely aggressive SCCs (RDEB-SCC), which represent the first cause of death in these patients. The genetic determinants of RDEB-SCC do not exhaustively explain its unique behavior as compared to low-risk, ultraviolet-induced SCCs in the general population. On the other hand, a growing body of evidence points to the key role of tumor microenvironment in initiation, progression and spreading of RDEB-SCC, as well as of other, less-investigated, EB-related SCCs (EB-SCCs). Here, we discuss the recent advances in understanding the complex series of molecular events (i.e., fibrotic, inflammatory, and immune processes) contributing to SCC development in EB patients, cross-compare tumor features in the different EB subtypes and report the most promising therapeutic approaches to counteract or delay EB-SCCs.

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Section: Dystrophic Ebmentioning

confidence: 95%

Section: Dystrophic Ebmentioning

confidence: 99%

Epidermolysis Bullosa-Associated Squamous Cell Carcinoma: From Pathogenesis to Therapeutic Perspectives

Condorelli

Dellambra

Logli

et al. 2019

IJMS

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“…RDEB‐SCC lines have been used in biomarker searches for early tumor detection 32 . An RDEB‐SCC line was cultured with conditioned media from RDEB patient or matched‐donor fibroblasts.…”

Section: Resultsmentioning

confidence: 99%

Role of transforming growth factor‐β1 in recessive dystrophic epidermolysis bullosa squamous cell carcinoma

Twaroski

Chen

Pickett‐Leonard

et al. 2021

Experimental Dermatology

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Squamous cell carcinoma (SCC) develops in more than 80% of individuals with the skin blistering disorder recessive dystrophic epidermolysis bullosa (RDEB). In contrast with UV‐induced SCC, RDEB‐SCC results from skin damage and has a high proliferative and metastatic rate with 5‐year survival near zero. Our objective is to determine the mechanisms underlying the increased metastatic tendencies of RDEB‐SCC. RDEB‐SCC cultured cell lines were treated with RDEB and non‐RDEB fibroblast conditioned media and assayed for migration and invasion with and without small molecule inhibitors for TGFβ and other downstream signal transduction pathways. TGFβ1 secreted by RDEB dermal fibroblasts has been found to induce migration and invasion and to increase expression of epithelial‐to‐mesenchymal transition markers in an RDEB‐SCC line. These effects were reversed upon inhibition of TGFβ signalling and its downstream pathways MEK/ERK, P38 kinase and SMAD3. A number of small molecule inhibitors for these pathways are in different phases of various clinical trials and may be applicable to RDEB‐SCC patients. Studying the mechanisms of the extreme form RDEB‐SCC may inform studies of other types of SCC, as well as lead to better therapies for RDEB patients.

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“…Current research strategies of the EB House Austria include CRISPR/Cas9-based technologies to correct COL7A1 and COL17A1 mutations and restore functional protein expression in keratinocytes [26]. Additional important research topics are the identification of extracellular vesicles with tumor-specific transcripts and tumor-specific miRNA molecules as both diagnostic markers (liquid biopsy) and as a therapeutic target for the highly aggressive EB squamous cell carcinoma [27,28], and the generation of a humanized mouse model as a clinically relevant platform for testing immunomodulatory therapeutic approaches and for analysis of gene therapy-associated immune reactions [29].…”

Section: Eb Research Unitmentioning

confidence: 99%

EB (epidermolysis bullosa)‐House Austria: Pioneering work for the care of patients with rare diseases

Prodinger

Laimer

Bauer

et al. 2020

J Deutsche Derma Gesell

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Summary The care of patients with epidermolysis bullosa (EB) poses a major challenge due to the rarity, heterogeneity and complexity of the disease as well as the occurrence of numerous primary and secondary extracutaneous manifestations, causing a significant morbidity and mortality. Specialized treatment centers are essential for offering these patients adequate care, including individual, interdisciplinary coordinated treatments according to current medical standards, and access to innovative therapeutic options. Against this background, the EB House Austria was founded in 2005 and designated the first national center of expertise for genodermatoses with a focus on EB in 2017. In the same year, it became a member of the European Reference Network for Rare Skin Diseases (ERN Skin). The pillars of this institution (outpatient clinic, research unit, academy, clinical study center) interact closely with each other, with numerous national and international clinical and scientific partners, as well as with patients and their relatives via the DEBRA Austria patient group. The development of the EB House Austria as a reference center is characterized by a long‐term pioneering work, which in turn could pave the way for the optimization of care for comparable diseases as well as general care structures.

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Extracellular Vesicles as Biomarkers for the Detection of a Tumor Marker Gene in Epidermolysis Bullosa-Associated Squamous Cell Carcinoma

Cited by 16 publications

References 13 publications

Epidermolysis Bullosa-Associated Squamous Cell Carcinoma: From Pathogenesis to Therapeutic Perspectives

Epidermolysis Bullosa-Associated Squamous Cell Carcinoma: From Pathogenesis to Therapeutic Perspectives

Role of transforming growth factor‐β1 in recessive dystrophic epidermolysis bullosa squamous cell carcinoma

EB (epidermolysis bullosa)‐House Austria: Pioneering work for the care of patients with rare diseases

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