Baj-Krzyworzeka M, Mytar B, Weglarczyk K, Szatanek R, Kijowski J, Siedlar M
Department of Clinical Immunology, Institute of Paediatrics, Jagiellonian University Medical College, Cracow, Poland.
Department of Transplantology, Institute of Paediatrics, Jagiellonian University Medical College, Cracow, Poland.
Folia Biol (Praha). 2020;66(3):104-110. doi: 10.14712/fb2020066030104.
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.
癌症发展是一个高度复杂的过程，其中肿瘤生长依赖于其血管生成系统的发育。为了支持自身生长，肿瘤细胞会显著改变其微环境。肿瘤造成的此类改变之一是刺激内皮细胞迁移和增殖。越来越多的证据表明，肿瘤细胞分泌的细胞外囊泡（EVs，肿瘤衍生的EVs，TEVs）可被视为具有影响靶细胞生物学活性潜力的“信使”。TEVs与不同细胞类型的相互作用以自分泌和旁分泌方式发生，并可能导致后者功能的改变，例如促进运动性、增殖等。本研究分析了源自人胰腺腺癌细胞系（HPC - 4，TEVHPC）的EVs在体外的促血管生成活性及其在体内对严重联合免疫缺陷（SCID）小鼠基质胶基质血管化的影响。TEVHPC增强了HPC - 4细胞的增殖并诱导其运动性。此外，TEVHPC在体外刺激人脐静脉内皮细胞（HUVEC）的增殖和迁移。另外，TEVHPC影响HUVEC细胞促血管生成因子（IL - 8、VEGF）的分泌，并在体内支持基质胶基质血红蛋白化。这些数据表明，TEVs可能以自分泌方式支持肿瘤增殖，并可能支持肿瘤的血管化。所呈现的数据与肿瘤细胞自身能够通过TEVs调节微环境以最大化其生长潜力的理论一致。
