Cathepsin L Induces Proangiogenic Changes in Human Omental Microvascular Endothelial Cells via Activation of the ERK1/2 Pathway

Current Cancer Drug Targets
Md Zahidul Islam PranjolJacqueline L Whatmore

Abstract

Metastasis still remains the major cause of therapeutic failure, poor prognosis and high mortality in epithelial ovarian cancer (EOC) patients. Previously, we showed that EOC cells secrete a range of factors with potential pro-angiogenic activity, in disease-relevant human omental microvascular endothelial cells (HOMECs), including the lysosomal protease cathepsin L (CathL). Thus, the aim of this study was to examine potential pro-proliferative and pro-migratory effects of CathL in HOMECs and the activated signalling pathways, and whether these proangiogenic responses are dependent on CathL-catalytic activity. HOMECs proliferation was investigated using WST-1, BrdU and CyQUANT assays. Cell migration was examined using a Cultrex Cell 96 transwell migration assay. Enzyme activity was assayed at various pHs using the CathL-specific fluorogenic substrate FY-CHO. Activation of cell signalling pathways was tested using a commercially available phosphokinase array and intact cellbased ELISAs. We showed for the first time that CathL has a potent pro-proliferative and pro-migratory effect on HOMECs. For instance, CathL significantly increases HOMEC proliferation (134.8±14.7% vs control 100%) and migration (146.6±17.3% vs control 100%). ...Continue Reading

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Citations

Jul 5, 2019·Journal of Translational Medicine·Md Zahidul I PranjolJacqueline L Whatmore
Oct 17, 2020·Tissue Engineering. Part a·Ariana D Suarez-MartinezWalter Lee Murfee
Dec 18, 2021·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Surinder M Soond, Andrey A Zamyatnin

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