A Disintegrin and Metalloprotease 10 Expressions Modulate Potential Metastatic and Thrombus Formation in Pancreatic Carcinoma.

Abstract

Background:Clinical investigations repurposing a disintegrin and metalloproteases 10 (ADAM10) as metastatic and thrombus marker have achieved encouraging results, but the mechanism behind this association remains unclear.Methods:This study was carried out in NingXia and Wuhan, China from 2017 to 2021. The effects of ADAM10 expression on the metastatic and thrombus-associated genes: tissue factor (TF), P-selectin glycoprotein ligand-1 (PSGL-1), cathepsin G (CTSG) and mucin 1 (MUC1) were examined by immunofluorescence, qRTPCR and Western blotting analysis. Metastatic and thrombotic behaviors were evaluated using NODSCID mouse model.Results:The ADAM10 expression controlled the migration and invasion of pancreatic carcinoma cell-1(PANC-1), and significantly regulated the metastatic and thrombus-associated genes (P<0.05). ADAM10 and MUC1 were regulated and aberrantly expressed by a dependent mechanism. Moreover, ADAM10 expression induced the progression of adenocarcinoma cells and thrombus formation in vivo.Conclusion:Regulation of ADAM10 expression in cancer cells might effectively pave the way for a more potent anti-metastatic and anti-thrombotic approach and could regulate the invasion and migration of cancer cells.