A possible role of CD46 for the protection in vivo of human renal tumor cells from complement-mediated damage

It is still unclear which membrane-bound regulatory proteins (mCRP) are imp ortant in vivo to protect tumor cells from complement-mediated damage. To a ddress this question, the expression levels of CD46, CD55, and CD59 were me asured semi-quantitatively in situ on renal cell carcinomas and compared wi th the expression level and cellular distribution of these mCRP in proximal tubuli within each patient (n = 31). It was also determined whether the ex pression of mCRP on tumor cells is associated with deposition of C3d and C5 b-9. CD46 expression was decreased on tumor cells; in contrast, CD55 was ex pressed on tumor cells (12 out of 31 samples), while it was not detected on proximal tubular epithelial cells (PTEC). Also, expression of CD59 on tumo r cells was increased as compared with its expression on PTEC. Furthermore, the localization on the cell surface of mCRP as observed on PTEC was alter ed on tumor cells. Because expression of mCRP may limit a complement-mediat ed anti-tumor response, we determined whether complement deposition was ass ociated with the expression level of CD46, CD55, and CD59. The presence of C3d on tumor cells was associated with a low expression level of CD46 (p < 0.02). The expression level of CD46 was also associated with a low tumor st age lo (p < 0.04). The results suggest that in vivo CD46 plays a role in th e protection of human renal tumor cells from complement-mediated injury.