The regulatory effect of hyaluronan on human mesenchymal stem cells' fate modulates their interaction with cancer cells in vitro.

Metastatic spread of cancer cells into a pre-metastatic niche is highly dependent on a supporting microenvironment. Human bone marrow-derived mesenchymal stem cells (bmMSCs) contribute to the tumor microenvironment and promote cancer metastasis by inducing epithelial-to-mesenchymal transition and immune evasion. The underlying mechanisms, however, are incompletely understood.

Dose- and time-dependent effects of hyaluronidase on structural cells and the extracellular matrix of the skin.

Introduction: Hyaluronic acid (hyaluronan; HA) is an essential component of the extracellular matrix (ECM) of the skin. The HA-degrading enzyme hyaluronidase (HYAL) is critically involved in the HA-metabolism. Yet, only little information is available regarding the skin's HA-HYAL interactions on the molecular and cellular levels.

Concomitant DNA methylation and transcriptome signatures define epidermal responses to acute solar UV radiation.

The simultaneous analysis of different regulatory levels of biological phenomena by means of multi-omics data integration has proven an invaluable tool in modern precision medicine, yet many processes ultimately paving the way towards disease manifestation remain elusive and have not been studied in this regard. Here we investigated the early molecular events following repetitive UV irradiation of in vivo healthy human skin in depth on transcriptomic and epigenetic level. Our results provide first hints towards an immediate acquisition of epigenetic memories related to aging and cancer and demonstrate significantly correlated epigenetic and transcriptomic responses to irradiation stress.

Intra-Patient Heterogeneity of Circulating Tumor Cells and Circulating Tumor DNA in Blood of Melanoma Patients.

Despite remarkable progress in melanoma therapy, the exceptional heterogeneity of the disease has prevented the development of reliable companion biomarkers for the prediction or monitoring of therapy responses. Here, we show that difficulties in detecting blood-based markers, like circulating tumor cells (CTC), might arise from the translation of the mutational heterogeneity of melanoma cells towards their surface marker expression. We provide a unique method, which enables the molecular characterization of clinically relevant CTC subsets, as well as circulating tumor DNA (ctDNA), from a single blood sample.

Inhibition of the hyaluronan matrix enhances metabolic anticancer therapy by dichloroacetate in vitro and in vivo.

Background And Purpose: Aerobic glycolysis is a unique feature of tumour cells that entails several advantages for cancer progression such as resistance to apoptosis. The low MW compound, dichloroacetate, is a pyruvate dehydrogenase kinase inhibitor, which restores oxidative phosphorylation and induces apoptosis in a variety of cancer entities. However, its therapeutic effectiveness is limited by resistance mechanisms.