Adipocyte-activated oxidative and ER stress pathways promote tumor survival in bone via upregulation of Heme Oxygenase 1 and Survivin.

ABSTRACT: Metastatic tumor cells engage the local tumor microenvironment and activate specific pro-survival mechanisms to thrive and progress in the harsh bone marrow niche. Here we show that the major contributors to the survival of carcinoma cells that have colonized the bone marrow are the adipocyte-induced oxidative stress and ER stress pathways. We demonstrate that upon exposure to adipocyte-rich environments in vitro or in vivo, bone-trophic prostate and breast tumor cells upregulate the oxidative stress enzyme, HO-1. We also show that HO-1 levels are significantly increased in human metastatic prostate cancer tissues and that stable HO-1 overexpression in tumor cells promotes growth and invasiveness. Co-incident with the adipocyte-induced expression of HO-1, there is an upregulation of ER cha

SUBMITTER: Herroon MK 

PROVIDER: S-EPMC5758829 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature