Endothelin-1 promotes survival and chemoresistance in chronic lymphocytic leukemia B cells through ETA receptor.

ABSTRACT: The endothelin axis, comprising endothelins (ET-1, ET-2 and ET-3) and their receptors (ET(A)R and ETBR), has emerged as relevant player in tumor growth and metastasis. Here, we investigated the involvement of ET-1/ET(A)R axis in chronic lymphocytic leukemia (CLL). CLL cells expressed higher levels of ET-1 and ETA receptor as compared to normal B cells. ET-1 peptide stimulated phosphoinositide-3-kinase and mitogen-activated protein kinase signaling pathways, improved survival and promoted proliferation of leukemic cells throughout ET(A)R triggering. Moreover, the blockade of ET(A)R by the selective antagonist BQ-123 inhibited the survival advantage acquired by CLL cells in contact with endothelial layers. We also found that blocking ET(A)R via BQ-123 interferes with ERK phosphorylation and

SUBMITTER: Maffei R 

PROVIDER: S-EPMC4046988 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature