Proangiogenic effects of tumor cells on endothelial progenitor cells vary with tumor type in an in vitro and in vivo rat model

Abstract

Endothelial progenitor cells (EPCs) contribute to neovascularization in tumors. However, the relationship of EPCs and tumor-induced angiogenesis still remains to be clarified. The present study aimed at investigating the influence of 4 different tumor types on angiogenic properties of EPCs in an in vitro and in vivo rat model. It could be demonstrated that in vitro proliferation, migration, and angiogenic abilities and genetic modifications of EPCs are controlled in a tumor-type–dependent manner. The proangiogenic effect of mammary carcinoma, osteosarcoma, and rhabdomyosarcoma cells was more pronounced compared to colon carcinoma cells. Coinjection of encapsulated tumor cells, especially mammary carcinoma cells, and EPCs in a rat model confirmed a contributing effect of EPCs in tumor vascularization. Cytokines secreted by tumors such as monocyte chemoattractant protein 1, macrophage inflammatory protein 2, and TNF-related apoptosis-inducing ligand play a pivotal role in the tumor cell–EPC interaction, leading to enhanced migration and angiogenesis. With the present study, we were able to decipher possible underlying mechanisms by which EPCs are stimulated by tumor cells and contribute to tumor vascularization. The present study will contribute to a better understanding of tumor-induced vascularization, thus facilitating the development of therapeutic strategies targeting tumor-EPC interactions.