Department of Plastic and Hand Surgery, Laboratory for Tissue Engineering and Regenerative Medicine, University Hospital of Erlangen, Friedrich‑Alexander University Erlangen‑Nürnberg (FAU), D‑91054 Erlangen, Germany.
Oncol Rep. 2019 Jul;42(1):350-360. doi: 10.3892/or.2019.7143. Epub 2019 May 2.
Adequate vascularization is pivotal for tumor progression and metastasis. Tumor angiogenesis is based on a sequence of interactions between the tumor and surrounding cells and the extracellular matrix. It is widely known that a tumor can influence and control its surroundings to create favorable conditions for further growth. To investigate the influence of various tumor types on endothelial cells (ECs), an in vitro rat cell model was used and rat liver EC52 cells were co‑cultured with conditioned medium derived from breast cancer MCR86, osteosarcoma ROS‑1, colon cancer CC531 and rhabdomyosarcoma R1H cell lines. In a distinct tumor‑type‑dependent manner, the EC52 cells exhibited changes in their function and gene expression. In all functional cell culture assays (proliferation, migration, transmigration, invasion and tube formation) the breast cancer cells exerted a significant effect on the angiogenic abilities of the ECs. When comparing the various tumor cell types, only the breast and colon cancer cells led to a significant stimulation of the EC migration and invasion. Proliferation, migration, invasion and tube formation were not or only hardly influenced by the osteosarcoma or rhabdomyosarcoma cells. Similarly, the breast and colon cancer cells exhibited the strongest influence on the upregulation of EC angiogenic genes, including the ones encoding vascular endothelial growth factor A, platelet and endothelial cell adhesion molecule 1, fibroblast growth factor 2, Von Willebrand factor, C‑X‑C motif chemokine ligand 12 and tyrosine kinase with immunoglobulin‑like and EGF‑like domains 1. Therefore, it is hypothesized that tumor cells enhance the angiogenic properties of ECs, including proliferation, migration, invasion and tube formation in a tumor‑type‑dependent manner. This is likely based on the upregulation of pro‑angiogenic genes in ECs induced by varying cytokine secretion signatures of tumor cells.
充分的血管生成对于肿瘤的进展和转移至关重要。肿瘤血管生成基于肿瘤与周围细胞和细胞外基质之间的一系列相互作用。众所周知，肿瘤可以影响和控制其周围环境，为进一步生长创造有利条件。为了研究各种肿瘤类型对内皮细胞（EC）的影响，使用了体外大鼠细胞模型，并将大鼠肝 EC52 细胞与乳腺癌 MCR86、骨肉瘤 ROS-1、结肠癌 CC531 和横纹肌肉瘤 R1H 细胞系的条件培养基共培养。以明显依赖于肿瘤类型的方式，EC52 细胞的功能和基因表达发生了变化。在所有功能细胞培养测定（增殖、迁移、透化、侵袭和管形成）中，乳腺癌细胞对 EC 的血管生成能力产生了显著影响。在比较各种肿瘤细胞类型时，只有乳腺癌和结肠癌细胞导致 EC 迁移和侵袭的显著刺激。增殖、迁移、侵袭和管形成不受或仅受骨肉瘤或横纹肌肉瘤细胞的影响。同样，乳腺癌和结肠癌细胞对 EC 血管生成基因的上调表现出最强的影响，包括编码血管内皮生长因子 A、血小板和内皮细胞黏附分子 1、成纤维细胞生长因子 2、血管性血友病因子、C-X-C 基序趋化因子配体 12 和含免疫球蛋白和表皮生长因子样结构域的酪氨酸激酶 1 的基因。因此，假设肿瘤细胞增强了 EC 的血管生成特性，包括增殖、迁移、侵袭和管形成，这在一定程度上依赖于肿瘤细胞不同的细胞因子分泌特征诱导的 EC 中促血管生成基因的上调。
