Cd93, also known as complement protein 1 q subcomponent receptor C1qR1 or C1qRp, is a transmembrane glycoprotein encoded by a gene on 20p11.21, consisting of 652 amino acids. It exists in soluble (sCD93) and membrane-bound forms. Cd93 is mainly expressed on endothelial cells, where it is key in promoting angiogenesis in both physiological and disease states, such as age-related macular degeneration and tumor angiogenesis. It is also expressed in hematopoietic stem cells, cytotrophoblast cells, platelets, and many immune cells, thus involved in modulating inflammatory-associated diseases and playing a role in cardiovascular disease development [1].

In CD93 -/- mice, primary melanoma growth was hampered, but metastatic dissemination increased, associated with disrupted endothelial cell junctions and elevated matrix metalloprotease 9 expression at the metastatic site. CD93 directly interacted with VEGFR2, and its absence led to VEGF-induced hyperphosphorylation of VEGFR2 in endothelial cells. Antagonistic anti-VEGFR2 antibody therapy rescued endothelial barrier function and reduced the metastatic burden in CD93 -/- mice to wild-type levels, revealing a key role of CD93 in maintaining vascular integrity in metastatic cancer [2]. Mice lacking Cd93 in group 3 innate lymphoid cells (ILC3s) exhibited impaired IL-22 production and aggravated colonic inflammation in experimental colitis, indicating that an IL-17D-CD93 axis regulates ILC3 function to preserve intestinal homeostasis [3].

In conclusion, Cd93 is crucial for angiogenesis, maintaining vascular integrity, and regulating immune-related cell functions. Gene knockout mouse models have been instrumental in revealing its role in metastatic cancer and intestinal inflammation. These findings suggest that Cd93 could be a potential therapeutic target for diseases related to angiogenesis, inflammation, and cancer metastasis.