This study provides the first evidence of an association between the ET-1 gene SNPs and haplotypes and the risk of chemoresistant pediatric OS, potentially adding new insights into the pathophysiology and treatment of chemoresistant OS.
The mRNA and the secreted protein levels of ET-1 in primary OS cell cultures (POCCs) established from surgically resected primary OS in the rs1800541 TT homozygotes were higher than those from the TG heterozygotes (P<0.05), who in turn showed higher ET-1 mRNA and secreted ET-1 levels than the GG homozygotes (P<0.05).
Transwell(®) cell invasion assays showed OS-III cells had a greater migrated cell number than OS-II cells, which could be abrogated by ET(A) receptor antagonist BQ123 (100 pmol/L), but not ET(B) receptor antagonist BQ788 (1 μmol/L); exogenous ET-1 dose-dependently promoted OS cell migration, which could be inhibited by BQ123 (100 pmol/L).