%0 Journal Article
%T Factors released by the tumor far microenvironment are decisive for pancreatic adenocarcinoma development and progression
%A Daniel Closa
%A Juan L. Iovanna
%J Archive of "Oncoimmunology".
%D 2017
%R 10.1080/2162402X.2017.1358840
%X The REG3¦Â protein was identified more than 2 decades ago, but its role in PDAC development was only recently reported. In Pancreatic Ductal Adenocarcinoma (PDAC), REG3¦Â protein is expressed and released by the far microenvironment, which is situated out of the tumor, at the periphery of the tumor mass, and is part of the healthy peri-tumoral region. This compartment is completely unrelated to the classical microenvironment that corresponds to the intra-tumoral stoma. Clinically relevant, the far microenvironment, and the factors released by it, could be novel and original therapeutic targets for treating patients with a PDAC. In this way we recently demonstrated that REG3¦Â is an essential soluble factor necessary for PDAC development which is able to stimulate several simultaneous pro-tumoral mechanisms. We also find that secreted REG3¦Â boosts interactions between epithelial cells and immune cells by activating the CXCL12/CXCR4 signaling cascade, which facilitates tumor escape through evasion of immune surveillance, and promotes metastasis. In addition, REG3¦Â interfere the intercellular communication inside the tumor mediated by extracellular vesicles, resulting in relevant changes in macrophage phenotype or tumor cell migration. Therefore, we are proposing to call as near microenvironment to the classical microenvironment that is constituted by fibroblasts, inflammatory cells and fibers and located into the tumor, and as far microenvironment, which is constituted by the parenchymal non transformed cells located at the periphery of the tumor mass
%K pancreas cancer
%K Reg3beta
%K microenvironment
%K peri-tumoral region
%K pancreatitis
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674953/