MMP2 and obesity due to melanocortin 4 receptor deficiency: While in vitro studies have demonstrated that culture of EAC cells with VAT or in adipose conditioned medium results in up-regulation of markers of proliferation, invasion and metastasis such as MMP-2 and−9, and attenuates tumor suppressor p53 (78, 79), obesity is also associated with increased markers of epithelial to mesenchymal transition in EAC, highlighting the role of adipose-secreted factors in the pathogenesis of EAC in obesity (80).