Resistin potentiates chemoresistance and stemness of breast cancer cells: Implications for racially disparate therapeutic outcomes

Abstract

Breast cancer (BC) continues to be the most frequently diagnosed cancer in American women, which disproportionately affects women of African-American (AA) descent. Previously, we reported greater serum levels of resistin in AA BC patients relative to Caucasian-American (CA) patients, and established its role in growth and aggressiveness of breast tumor cells. Here we have investigated the role of resistin in BC-chemoresistance. MDA-MB-231 and MDA-MB-468 BC cells of CA and AA origin, respectively, were incubated with resistin prior to doxorubicin treatment. Our data suggest that resistin conferred chemoresistance to both BC cell lines; however, the effect on AA cells was more profound. Furthermore, the resistin-induced doxorubicin-resistance was shown to occur due to suppression of apoptosis. Resistin treatment also affected the stemness of BC cells, as suggested by reduced cell surface expression of CD24, induced expression of CD44 and ALDH1, and increased capability of cells to form mammospheres. Mechanistic studies revealed that resistin-induced chemoresistance, apoptosis and stemness of BC cells were mediated through STAT3 activation. Taken together, our findings provide novel insight into the role of resistin in BC biology, and strengthen its role in racially disparate clinical outcomes.

Putative tumor suppressor cytoglobin promotes aryl hydrocarbon receptor ligand–mediated triple negative breast cancer cell death

“…13 We and others have shown that certain AhR ligands induce apoptosis in TNBC cells. 40,41 In this study, we observed that silencing CYGB reduced 5F 203-mediated apoptosis, caspase-3/-7 activation, LMP, and cathepsin B release. 39 Many cancers, including breast cancer, support their survival by deregulating apoptosis induced by therapies, which makes it paramount to understand the mechanism(s) used to evade cell death.…”

Drug-loaded exosomal preparations from different cell types exhibit distinctive loading capability, yield, and antitumor efficacies: a comparative analysis

“…[38][39][40] It is well established that treatment of cancer cells with DOX induces apoptosis. 37,[41][42][43] We observed that all the tested Exo-DOX formulations outperformed free DOX in cytotoxicity toward PCCs. This could be due to the fact that drug efflux pumps actively pumpout DOX from the cancer cells.…”

Elevated circulatory levels of leptin and resistin impair therapeutic efficacy of dacarbazine in melanoma under obese state

“…In addition, since we observed a trend of tumor progression and impaired therapeutic outcome in ob/ob mice (which lack functional leptin) as compared to their wild-type counterparts, obesity-associated factors (other than leptin) could also influence tumor progression and the impairment of chemotherapy. As serum level of resistin is very high in ob/ob mice, and we observed in vitro that resistin is equally partly responsible for causing impairment in the efficacy of DTIC, it is conceivable that even in the absence of leptin, resistin could be involved in impairing the efficacy of DTIC in ob/ob mice, as resistin is very well known to induce drug-resistant phenotype in various cancers [ 14 , 15 , 49 , 50 ]. Although, our in vitro results established the fact that both leptin and resistin are involved in impairing the response of melanoma cells to DTIC, it is difficult to validate their role in vivo due to lack of resistin knockout animals as well as resistin neutralizing antibody.…”