The role of CD55 in protecting the tumour environment from complement attack.

CD55 is a complement regulatory protein expressed by cells to protect them from bystander killing by complement. CD55 is over-expressed 2-100-fold on tumour cells and is deposited in large amounts within tumour matrix. Vascular endothelial growth factor (VEGF) produced by tumours to stimulate angiogenesis, also up-regulates endothelial cell surface expression of CD55 and stimulates the release of matrix degrading metalloproteinases. This study investigated the effects of VEGF on CD55 deposition into matrix and the release of CD55 by metalloproteinases. In contrast to inflammatory cytokines, CD55 was up-regulated by VEGF at the cell surface and within the extracellular matrix (ECM). Interestingly, human umbilical vein endothelial cells (HUVEC) exposed to VEGF released similar amounts of CD55 into the ECM as a tumour cell line expressing 50-fold higher level of CD55 on its cell surface. Furthermore, in contrast to earlier studies, both tumour and HUVEC-derived CD55 was functionally active. However, in contrast to papain that degrades CD55, and collagenase that fails to release CD55, MMP-7 released intact CD55 from ECM. This suggests that it may have a further role to play in protecting cells during inflammation and invasion.