Adiponectin inhibits mouse mammary tumor growth and reduced tumor-induced hematopoiesis

Abstract

Adiponectin, one of the most abundant plasma protein produced in adipose tissue, has been shown to be decreased in the plasma of patients with various types of cancer suggesting that adiponectin may be involved in the pathogenesis of tumor progression. In addition, studies have shown that this adipokine exhibit a suppressive effect on different types of malignancy. However, the role of adiponectin in tumor progression or tumor immunity remains unknown. In this study, we assessed the effect of adiponectin on murine breast cancer progression. We implanted murine breast cancer cells (EMT6) breast cancer cells subcutaneously into the tight flank of syngeneic mice. Local administration of adiponectin to tumor tissue decreased tumor mass in a dose-dependent manner. Since intratumoral injection of lipopolysaccharide (LPS), the major component of endotoxin, is known to inhibit tumor growth, the observed anti-tumor effect of the recombinant adiponectin might be attributable to the contamination of low amounts of bacterial endotoxin. We showed that intratumoral injection of low dose LPS failed to inhibit tumor growth and heat inactivation or protease treatment completely abrogated the cytokine’s ability to induce IL-12p35 expression in mouse bone marrow-derived dendritic cells clearly demonstrating that the observed anti-tumor effect of recombinant adiponectin is not due to LPS contamination. Our data clearly suggest that adiponectin exerts anti-tumor effects in the breast cancer model of mice via reduction of tumor-induced hematopoiesis and intratumoral injection of adiponectin may be a new strategy for the treatment of established breast cancer.