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Deschner, J.

Publications and source records attributed to Deschner, J..

2 recordsLinked to original sources
bioRxiv2026

In vitro effects of tensile strain on cancer-associated and matched normal fibroblasts derived from oral squamous cell carcinoma: an exploratory study

BackgroundMechanical forces, particularly tensile stress, influence tumor progression by modulating cancer-associated fibroblast (CAF) behaviour and extracellular matrix remodelling, yet their role in oral cancer remains insufficiently defined. To our knowledge, this is the first study investigating in vitro tensile stress responses in CAF and normal fibroblasts (NF) derived from oral squamous cell carcinoma (OSCC). ObjectiveTo assess how tensile stress affects fibroblast gap closure, proliferation, metabolic activity, and paracrine signalling relevant to tumor-stroma interactions. MethodsCAFs and NFs were isolated from OSCC tissue and matched healthy mucosa and exposed to cyclic tensile strain (3%, 0.02 Hz, 96 h) using the FX-6000T system. Gap closure was assessed by wound-healing assay, proliferation by cell counting, metabolic activity by AlamarBlue, and paracrine effects on A549 tumor cell gap closure using fibroblast-conditioned supernatants. ResultsTensile loading significantly increased CAF gap closure capacity compared with both stimulated NFs (p<0.0001) and unstimulated CAF controls (p=0.0167). Metabolic activity showed a non-significant trend toward higher values in CAFs. Proliferation did not differ between groups up to 48 h, arguing against a major early contribution of proliferation to the observed group differences in the fibroblast scratch assays; however, because proliferation was not inhibited and was not quantified beyond 48 h, later time points should be interpreted conservatively as composite gap closure. Supernatants from mechanically stimulated CAFs increased A549 gap closure by [~]40% compared with non-stimulated controls (p=0.0485), whereas stimulated NFs did not enhance the tumor cells capacity to close the cell-free gap. ConclusionsTensile strain was associated with increased fibroblast gap closure and enhanced gap-closure-promoting paracrine effects of oral CAFs under the conditions tested. These exploratory findings support the concept that biomechanical cues can modulate CAF functional behaviour in OSCC. Given the limited cohort size and inter-patient variability, these results should be interpreted as hypothesis-generating and require confirmation in larger studies. Mechanistic pathways were not interrogated in this study and should be addressed in future work using more complex tumor-stroma models. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=127 SRC="FIGDIR/small/737904v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@d275c6org.highwire.dtl.DTLVardef@13249c5org.highwire.dtl.DTLVardef@8964b9org.highwire.dtl.DTLVardef@33e767_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗
bioRxiv2026

E-cadherin maintains oral Langerhans cell barrier surveillance to preserve microbiota-dependent immune homeostasis

Langerhans cells (LC) are specialized antigen-presenting cells that form a dense immune surveillance network within the oral epithelium. There, they continuously interact with epithelial cells and the resident microbiota to maintain mucosal homeostasis. A defining feature of LC is their highly dendritic morphology, which enables efficient sampling of the environment at barrier surfaces. Although E-cadherin-mediated adhesion has been implicated in LC-epithelial cell interactions, its role in oral LC biology and periodontal immune homeostasis remains elusive. Here, we investigated the function of E-cadherin on oral LC using CD11c-specific E-cadherin-deficient (CD11c-EcadDEL) mice. Loss of E-cadherin profoundly altered LC morphology throughout the oral mucosa, resulting in reduced dendrite formation and impaired dendrite extension towards the epithelial surface, thereby disrupting interaction with the oral microbiota. While the total number of LC remained unchanged, E-cadherin deficiency significantly altered the relative distribution of LC subsets, characterized by reduced LC1 and increased LC2 populations. E-cadherin-deficiency was associated with pronounced oral dysbiosis, characterized by increased bacterial burden and microbial diversity, as well as a shift away from the commensal-dominated community, particularly through the loss of protective lactobacilli. Transcriptome analysis of gingival tissue revealed inflammatory reprogramming marked by enrichment of NF-{kappa}B, TNF, IL-17, Toll-like receptor, and MAPK signaling pathways. Consistently, CD11c-EcadDEL mice exhibited increased IL-17A production in the gingiva, expansion of {beta} and {gamma}{delta} T cells, spontaneous age-dependent alveolar bone loss, and exacerbated inflammatory bone destruction in a model of ligature-induced periodontitis. In summary, our findings reveal that E-cadherin preserves oral LC dendrite organization and microbiota-dependent immune homeostasis, thereby limiting dysbiosis-driven inflammation and periodontal bone loss.

immunology↗