Targeting Breast Cancer Stem Cells In Triple Negative Breast Cancer.

摘要

Obesity is associated with higher incidence of triple negative breast cancer (TNBC) and drug resistance. We hypothesize that obesity effects on TNBC occur via leptin-signaling stimulation of breast cancer stem cells (BCSC), which could involve the activation of VEGFR-2/Notch axis. During the first year of the funding period we performed in vitro studies in human TNBC cell lines treated with leptin, and novel leptin receptor inhibitor bound to nanoparticles (IONPs-LPrA) alone, and combined with cisplatin (a chemotherapeutic) and Sunitinib (an inhibitor of VEGFR-2 kinase). Our data show that leptin increased cell proliferation and expression of BCSC markers in human TNBC that was accompanied by induction of mammosphere formation, reduced effectiveness of cisplatin and sunitinib and increased expression and activation of Notch.