HAS3 overexpression

Inhibiting TLR4 receptor decreased the cytokine expression induced by HAS3-MV3 EVs, suggesting TLR4-mediated activation after HAS3-MV3 EV exposure. Our results suggest that melanoma cell derived EVs induce mixed M1/M2 polarization of THP1 monocytes.

PEGPH20 may be useful for radiosensitization of pancreatic cancer but only in the subset of tumors with substantial hyaluronan accumulation. The response of the treatment may potentially be monitored by non-invasive imaging of the hemodynamic and metabolic changes in the tumor microenvironment.

Response of Vector-only (EV), HAS3-overexpressing (HAS3) or HAS3-knockdown (HAS3-KO) transfectants of 786-O and Caki-1 cells, primary RCC spheroids and endothelial cells co-cultured with these transfectants to MU combined with Sorafenib (SF), Sunitinib or Everolimus was examined in proliferation, apoptosis, motility and invasion assays. This is the first study to demonstrate that HAS3 significantly predicts metastasis. By downregulating HAS3 expression, MU+SF combination effectively abrogates RCC growth and metastasis. HAS3 is a potential biomarker to predict clinical outcome in RCC patients.

Our study demonstrated that HAS3-mediated signaling activated by physiological concentrations of melatonin (>0.1 nmol/L) triggered significant N2a cell differentiation. These results provide molecular data with potential clinical relevance for therapeutic drug development.