RESUMO
Over the past decades, obesity has grown to epidemic proportions worldwide. It has been associated with an increased risk for different types of cancer. In addition, obesity has been associated with a poor prognosis, an increased risk of metastasis and mortality, and resistance to anti-cancer therapies. The pathophysiological mechanisms underlying the obesity-cancer connection have not yet been fully elucidated. However, this connection could result, at least in part, from the action of adipokines, whose levels are increased in obesity. Among these adipokines, evidence suggests leptin's critical role in linking obesity to cancer. In this review, we first summarize the current state of the literature regarding the implication of leptin in tumorigenic processes. Next, we focus on the effects of leptin on the anti-tumor immune response. Then, we discuss the influence of leptin on the efficiency of antineoplastic treatments and the development of tumor resistance. Finally, we highlight the use of leptin as a potential target for the prevention and treatment of cancer.
Assuntos
Antineoplásicos , Neoplasias , Humanos , Adipocinas , Antineoplásicos/farmacologia , Leptina/farmacologia , Neoplasias/complicações , Obesidade/patologiaRESUMO
To better understand the link between obesity and prostate cancer (PC) aggressiveness, we investigate the role of leptin, an obesity associated adipokine, and its receptor (Ob-R) in PC cells migration. The migration assay (Wound-healing) was used to study the leptin impact on DU-145 and PC3 cells lines. STAT3 activation was performed by Western Blot. E-cadherin expression was studied using fluorescence microscopy and Ob-R expression in PC and benign prostatic Hyperplasia (BPH) biopsies was assessed by RT-PCR. In this study we demonstrate that high dose of leptin promotes PC cells migration and EMT transition via the stimulation of STAT3 pathway. In addition, we report that although Ob-R mRNA is expressed by ADK and BPH resections biopsies, significant higher levels were observed for ADK patients. Finally, we found a positive association between Ob-R mRNA expression and worse PC prognosis. A better understanding of the molecular processes of leptin signaling is crucial for identifying appropriate approaches for treatment of obesity-related PC patients.