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.-An, R., Schmid, R., Klausing, A., Robering, J. W., Weber, M., Bäuerle, T., Detsch, R., Boccaccini, A. R., Horch, R. E., Boos, A. M., Weigand, A. Proangiogenic effects of tumor cells on endothelial progenitor cells vary with tumor type in an in vitro and in vivo rat model.

The Osteosarcoma Microenvironment: A Complex but Targetable Ecosystem

“…In Ewing sarcoma bone tumor, bone marrow EPC-induced vasculogenesis has been identified as an essential step of neovascularization and is crucial for tumor growth, with 10% of neo-vessels containing bone-marrow-derived cells [100]. In OS, a role for EPCs in neovascularization was also recently highlighted in an in vitro rat model, where co-injection of encapsulated OS cells with EPCs enhanced tumor vascularization [101]. In that case, OS rat tumor cells promoted migration and angiogenic properties of EPCs, through their specific secretome of angiogenesis-related factors (VEGF, TGF-β1, MCP-1, Activin A, and OPN).…”

Size matters—in vitro behaviour of human fibroblasts on textured silicone surfaces with different pore sizes

“…The medium was exchanged with 300 µl of DMEM high glucose and supplemented with 30 µl of the tetrazolium salt WST-8. Following 2 h of incubation, the absorption of 100 µl supernatant from each sample was measured at 450 nm with a reference wavelength of 600 nm (Multiskan GO; Thermo Fisher Scientific) [38].…”

Stammzellen in der Regenerativen Medizin – Translationale Hürden und Möglichkeiten zur Überwindung

“…Hier ist allerdings nochmal zu betonen, dass dieses kanzerogene Potential bisher nur in vitro gezeigt werden konnte. Weitere Studien, welche auf komplexeren Ansätzen beruhen, werden nur vereinzelt beschrieben [104,105]. Diese sind jedoch dringend benötigt, um die Sicherheit der klinischen Anwendung von extern kultivierten MSCs zu gewährleisten [106].…”