Targeting heparanase overcomes chemoresistance and diminishes relapse in myeloma.

ABSTRACT: In most myeloma patients, even after several rounds of intensive therapy, drug resistant tumor cells survive and proliferate aggressively leading to relapse. In the present study, gene expression profiling of tumor cells isolated from myeloma patients after sequential rounds of chemotherapy, revealed for the first time that heparanase, a potent promoter of myeloma growth and progression, was elevated in myeloma cells that survived therapy. Based on this clinical data, we hypothesized that heparanase was involved in myeloma resistance to drug therapy. In several survival and viability assays, elevated heparanase expression promoted resistance of myeloma tumor cells to chemotherapy. Mechanistically, this enhanced survival was due to heparanase-mediated ERK signaling. Importantly, use of the

SUBMITTER: Ramani VC 

PROVIDER: S-EPMC4811483 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature