Protumorogenic Potential of Pancreatic Adenocarcinoma-Derived Extracellular Vesicles.

Abstract

Cancer development is a highly complicated process in which tumour growth depends on the development of its vascularization system. To support their own growth, tumour cells significantly modify their microenvironment. One of such modifications inflicted by tumours is stimulation of endothelial cell migration and proliferation. There is accumulating evidence that extracellular vesicles (EVs) secreted by tumour cells (tumour-derived EVs, TEVs) may be regarded as "messengers" with the potential for affecting the biological activities of target cells. Interaction of TEVs with different cell types occurs in an auto- and paracrine manner and may lead to changes in the function of the latter, e.g., promoting motility, proliferation, etc. This study analysed the proangiogenic activity of EVs derived from human pancreatic adenocarcinoma cell line (HPC-4, TEVHPC) in vitro and their effect in vivo on Matrigel matrix vascularization in severe combined immunodeficient (SCID) mice. TEVHPC enhanced proliferation of HPC-4 cells and induced their motility. Moreover, TEVHPC stimulated human umbilical vein endothelial cell (HUVEC) proliferation and migration in vitro. Additionally, TEVHPC influenced secretion of proangiogenic factors (IL-8, VEGF) by HUVEC cells and supported Matrigel matrix haemoglobinization in vivo. These data show that TEVs may support tumour propagation in an autocrine manner and may support vascularization of the tumour. The presented data are in line with the theory that tumour cells themselves are able to modulate the microenvironment via TEVs to maximize their growth potential.