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To achieve successful vascular targeting in cancer, a better understanding of the molecular mechanisms that lead to tumour vascular abnormalities is required.  The transmembrane protein CD93 is highly expressed in the vasculature of several tumours including glioblastoma and has emerged as a potential anti-angiogenic target. This thesis work explores the mechanisms through which CD93 contributes to vascular function and facilitates tumour progression. In paper I, we identify that CD93 interacts with the extracellular matrix (ECM) glycoprotein multimerin-2, which stabilizes CD93 at the cell surface and anchors it to the ECM protein fibronectin. CD93 binds to integrinα5β1 and regulates the activity of integrinβ1 and fibronectin fibrillogenesis in vitro. Consistent with this, the tumor vessels of CD93^-/- mice bearing gliomas displayed an impaired integrinβ1 activity and fibronectin fibrillogenesis, suggesting that CD93-multimerin-2-fibronectin axis has an important role in tumour angiogenesis. In paper II, we explored the co-regulation of CD93 with other genes associated with glioblastoma vascular abnormalities. Using the publicly available Gliovis database for distinguished gene correlation analysis, we identified multimerin-2, fibronectin and angiopoietin-2 as candidate genes which are likely to be expressed with CD93 in glioblastoma vasculature. The expression of CD93, fibronectin and angiopoietin-2 was associated with high microvascular proliferation. Moreover, the presence of CD93 in a high proportion of the tumor vessels correlated with poor survival, suggesting that targeting CD93 can be beneficial for glioblastoma patients. In paper III, we explored the role of CD93 in the blood brain barrier (BBB) integrity. We demonstrate that CD93 regulates the activity of Rho-GTPases, thus stabilizing the endothelial junction molecules VE-cadherin and claudin-5 and preventing the internalization of VE-cadherin. Consistent with this, CD93^-/- mice displayed a compromised BBB and exhibited an increased vascular permeability. In paper IV, we further explored the consequences of endothelial barrier disruption upon CD93-deficiency in cancer. We demonstrate that CD93 binds to VEGFR2 and that the absence of CD93 enhances VEGF-induced VEGFR2 phosphorylation in vitro. Consistent with this, melanoma-bearing CD93^-/- mice displayed impaired vascular integrity and an enhanced MMP9 expression, leading to increased intravasation of tumour cells and increased metastatic spread. This phenotype was reversed to the wild-type level by inhibiting the VEGF-VEGFR2 signalling in CD93^-/- mice. Taken together, this thesis work reveals a key role of CD93 in regulating vascular maturation and stabilization in health and cancer, and unveils its contribution to tumour progression and metastasis.