Universidad Metropolitana, Sistema Universitario Ana G. Mendez
There is growing evidence supporting the role of stress in cardiovascular pathologies, cancer and other diseases. Several epidemiological and pre-clinical studies have suggested that altered behavioral states, such as chronic stress or depression, may accelerate growth of existing tumors. Our previous work has shown that sustained adrenergic signaling induces tumor cells to secrete elevated levels of pro-inflammatory cytokines, promote infiltration of pro-tumoral macrophages and increase tumor progression. Moreover, our data suggest that there is a significant correlation between macrophage infiltration and decreased survival among ovarian cancer patients. While the importance of adrenergic signaling in macrophage recruitment has been established, the role of adrenergic-induced tumor-associated macrophages (TAMs) in the ovarian tumor microenvironment remains poorly understood. Hence, we hypothesize that sustained adrenergic signaling induces TAMs to up-regulate pro-inflammatory networks that exacerbates the progression of ovarian cancer while CCR2/4 siRNA nanoparticles abrogate this effect. The objective of this proposal is to determine the role of TAMs on adrenergic induced ovarian cancer progression.