Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a hereditary skin disorder characterized by mechanical fragility of the skin, resulting in blistering and chronic wounds. The causative mutations lie in the COL7A1 gene. Patients suffering from RDEB have a high risk to develop aggressive, rapidly metastasizing squamous cell carcinomas (SCCs). Cutaneous RDEB SCCs develop preferentially in long-term skin wounds or cutaneous scars. Albeit being well differentiated, they show a more aggressive behavior than UV-induced SCCs. These findings suggest other contributing factors in SCC tumorigenesis in RDEB. Objective: To analyze factors contributing to RDEB tumorigenesis, we conducted a comprehensive gene expression study comparing a non-malignant RDEB (RDEB-CL) to a RDEB SCC cell line (SCCRDEB4) to achieve an overview on the changes of the gene expression levels in RDEB related skin cancer. Methods: We applied cDNA arrays comprising 9738 human expressed sequence tags (EST) with various functions. Selected results were verified by Real-time RT PCR. Results: Large-scale gene expression analysis revealed changes in the expression level of transforming growth factor β1 (TGFβ1) and several genes under the control of TGFβ for RDEB and SCCRDEB4 cell lines. Even untransformed RDEB keratinocytes show elevated levels of TGFβ1. Conclusion: Our findings demonstrate a prominent role of TGFβ-signaling in RDEB-related skin cancer. Once activated, TGFβ signaling either in response to wounding or in order to influence type VII collagen expression levels could facilitate cancer development and progression. Moreover, TGFβ signaling might also represent a potentially useful therapeutic target in this disease.
Epidermolysis bullosa (EB) is a group of hereditary skin disorders. Although each subtype is caused by mutations in genes encoding differentially located components of the skin, the resulting phenotype is similar. In this study, we investigated similarities in the gene expression profiles of each subtype on mRNA level. Type XVI collagen (COL16A1), G0/G1 switch 2 (G0S2), fibronectin (FN1), ribosomal protein S27A (RPS27A) and low density lipoprotein receptor (LDLR) were shown to exhibit corresponding changes in gene expression in all three EB subtypes. While COL16A1, G0S2 and FN1 are up-regulated, LDLR and RPS27A mRNA levels are decreased. These data indicate that EB cells seem to take measures increasing their mechanical stability. Apoptosis is likely to be exacerbated, and migratory potential appears to be elevated. Protein degradation is hampered, and the release of fatty acids and glycerol is restricted, probably to save energy. These commonalities might benefit existing EB treatment strategies or could help to reveal new starting points for the treatment of EB in the future.
We clearly demonstrate in vitro tumor cell selectivity of PPIX-accumulation over endothelial cells, MNCs and RBCs. Breast cancer cells are efficiently killed by PDT with minor depletion of MNCs. Our findings provide a basis for the PDT of blood samples for a future depletion of CTCs.
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