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

What is it about?

Endothelial progenitor cells (EPCs) participate in the neovascularization process in the development of tumors. Tumor cells regulate their environment by releasing cytokines, including activators and inhibitors. The imbalance of the molecules promotes new vessel formation to provide enough oxygen and nutrients for the growth of the tumor. We aimed to highlight the importance of studying tumor angiogenesis and testing the interaction of EPCs and different types of tumors. It could be demonstrated that the functional properties of EPCs, including proliferation, migration and angiogenic abilities were significantly enhanced under the effects of tumors. Besides, tumors up-regulated the pro-angiogenic genes and down-regulated the anti-angiogenic genes in EPCs. The enhancement of the functional and genetic properties of EPCs varied among different types of tumors. Further, we established a new cell carrier hydrogel composed of alginate and fibrin. The alginate/fibrin hydrogels could provide an optimal and biodegradable environment for three dimensional tumor engineering. For in vivo analysis, tumor cells with or without EPCs were encapsulated into the alginate/fibrin hydrogels and were injected subcutaneously in rats. Constructs with tumor cells co-injected with EPCs demonstrated a significantly higher vessel formation. Three cytokines, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), play an important role in this tumor cell-EPC interaction. Understanding the relationship of EPCs and tumor-induced angiogenesis could help to develop effective anti-angiogenic therapies of cancer.

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