Metastasis formation is a multistep process that involves cancer cell transmigration through tumor vessels and through the healthy vasculature of the affected organ. This process is limited by an intact vascular barrier formed by endothelial cells, ECM, and pericytes. In a publication in JCI Insight, researchers from HPA and Uppsala University studied the role of the protein CD93 in maintaining vascular integrity in metastatic cancers.

CD93 is an emerging target for antiangiogenic therapy due to its association with tumor angiogenesis, but it also regulates endothelial cytoskeletal organization and junctional stability, which could suggest a role in maintaining vascular integrity. In this study the role of CD93 related to vascular integrity in metastatic melanoma was investigated and the results show that CD93 forms a complex with VEGFR2 in endothelial cells and that CD93 deficiency leads to a hyperresponsiveness of VEGFR2 to VEGF stimulation. This destabilizes the primary tumor vasculature, facilitating the intravasation of tumor cells, and creates a permissive microenvironment at the site of metastasis.

These findings thus reveal CD93 to also have an important role in maintaining vascular integrity, which has implications for pathological angiogenesis and endothelial barrier function in metastatic cancer.

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