Vasculogenic Mimicry: A Potential Therapeutic Target for Chondrosarcoma Therapy

TL;DR

This paper explores vasculogenic mimicry in chondrosarcomas, identifying a potential new therapeutic target and a promising antiangiogenic peptide.

Contribution

The study is the first to document vasculogenic mimicry in human chondrosarcoma tissues and identifies uPAR as a key mediator.

Findings

Chondrosarcoma cells can form vascular-like structures in vitro, similar to endothelial cells.

The uPAR receptor is crucial for vasculogenic mimicry in chondrosarcomas.

The uPAR-derived peptide RI-3 inhibits vasculogenic mimicry, unlike bevacizumab.

Abstract

Chondrosarcomas (ChSs) are mesenchymal chemo- and radiation-resistant tumors, representing the second most frequently diagnosed bone sarcoma after osteosarcoma and 20% of all bone sarcomas. Most of ChS patients have a good prognosis after complete surgical resection. Conversely, patients with inoperable disease, due to the tumor location or metastatic dissemination, represent a great clinical challenge due to the lack of effective therapeutic options. In this study, to the best of our knowledge, we document, for the first time in human ChS tissues, the existence of CD-31- and Podoplanin-negative vascular-like channels containing red blood cells, allowing us to hypothesize the occurrence of vasculogenic mimicry (VM) in ChSs. By using patient-derived ChS cells and a stabilized ChS cell line, we demonstrate that ChS cells are able to form in vitro tubules apparently similar to those formed by endothelial cells. Further characterization of these vessels revealed the pivotal role of the Urokinase Plasminogen Activator Receptor (uPAR) in mediating the capability of ChS cells to form VM. Finally, we provide evidence that, unlike bevacizumab, which did not exert any effect, the uPAR-derived antiangiogenic peptide RI-3 behaves as a potent inhibitor of VM.

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