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Oncology letters

Tryptase promotes breast cancer angiogenesis through PAR-2 mediated endothelial progenitor cell activation.


PMID 30008831

Abstract

Mast cells have been demonstrated to accumulate around and within solid tumors of numerous types, and express a number of pro-angiogenic compounds, including tryptase. They may serve an early role in angiogenesis within developing tumors. In the present study, the role and mechanism of tryptase in the activation of endothelial progenitor cells (EPCs) in breast cancer angiogenesis were evaluated. Human umbilical cord blood EPCs were isolated and cultured. MB-MDA-231 breast cancer cells were then pretreated with tryptase, and the conditioned medium was collected. The effects of tryptase on the migratory and angiogenesis abilities of EPCs were determined using wound-healing and tube formation assays, respectively. The effect of tryptase on the proliferation of EPCs was detected using a Cell Counting Kit-8 assay. Alterations in proteinase activated receptor (PAR)-2, phosphorylated (p)-protein kinase B (AKT), p-extracellular signal-regulated kinase (p-ERK) and vascular endothelial growth factor receptor (VEGFR)-2 expression were analyzed, in tryptase or conditioned medium-treated EPCs, by western blot analysis and reverse transcription-quantitative polymerase chain reaction. It was confirmed that the EPCs expressed PAR-2; and that tryptase treatment promoted the migration and tube formation of EPCs. Treatment with a PAR-2 agonist had a similar effect to tryptase, whereas treatment with a tryptase inhibitor, APC366, or a PAR-2 inhibitor, SAM 11, inhibited the effect of tryptase treatment. Tryptase and PAR-2 agonists did not affect the rate of EPC proliferation. MB-MDA-231 cells also expressed PAR-2. Treatment with tryptase or conditioned medium increased the expression of PAR-2, p-AKT, p-ERK and VEGFR-2 in EPCs. In conclusion, tryptase activated EPCs via PAR-2-mediated AKT and ERK signaling pathway activation, thereby enhancing angiogenesis in breast cancer.

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