Tumor-type-dependent effects on the angiogenic abilities of endothelial cells in an in vitro rat cell model

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.