1. ESDN inhibits melanoma progression by blocking E-selectin expression in endothelial cells via STAT3
- Author
-
Francesca Orso, Désirée Baruffaldi, Daniela Taverna, Lorena Quirico, Guido Serini, Paola Defilippi, Federico Virga, Massimiliano Mazzone, Lei Nie, Elena Grassi, Daniela Dettori, Alberto Dalmasso, Donatella Valdembri, Mehran M. Sadeghi, Paolo Provero, Roberto Coppo, and Fabiana Clapero
- Subjects
STAT3 Transcription Factor ,0301 basic medicine ,Cancer Research ,Stromal cell ,Angiogenesis ,Article ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Adhesion ,Cimetidine ,ESDN ,Melanoma metastasis ,Tumor microenvironment ,E-selectin ,Tumor Microenvironment ,medicine ,Animals ,Humans ,Cell adhesion ,STAT3 ,Melanoma ,biology ,Chemistry ,Endothelial Cells ,Membrane Proteins ,medicine.disease ,Extravasation ,Disease Models, Animal ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Disease Progression ,Cancer research ,biology.protein ,E-Selectin - Abstract
An interactive crosstalk between tumor and stroma cells is essential for metastatic melanoma progression. We evidenced that ESDN/DCBLD2/CLCP1 plays a crucial role in endothelial cells during the spread of melanoma. Precisely, increased extravasation and metastasis formation were revealed in ESDN-null mice injected with melanoma cells, even if the primary tumor growth, vessel permeability, and angiogenesis were not enhanced. Interestingly, improved adhesion of melanoma cells to ESDN-depleted endothelial cells was observed, due to the presence of higher levels of E-selectin transcripts/proteins in ESDN-defective cells. In accordance with these results, anticorrelation was observed between ESDN and E-selectin in human endothelial cells. Most importantly, our data revealed that cimetidine, an E-selectin inhibitor, was able to block cell adhesion, extravasation, and metastasis formation in ESDN-null mice, underlying a major role of ESDN in E-selectin transcription upregulation, which according to our data, may presumably be linked to STAT3. Based on our results, we propose a protective role for ESDN during the spread of melanoma and reveal its therapeutic potential. ispartof: CANCER LETTERS vol:510 pages:13-23 ispartof: location:Ireland status: published
- Published
- 2021
- Full Text
- View/download PDF