Human poliovirus receptor CD155 enhances the proliferation of Ras gene-mutant cells.

2811 Human poliovirus receptor CD155 serves as an entry receptor for poliovirus in human and is a member of immunoglobulin superfamily. CD155 is also the homolog of Nectin-like molecule-5 (Necl-5), which works as an adhesion molecule of the cells in mice. CD155 was shown to be overexpressed in many human cancer cells, but its roles and significance are not clear. Recently, it was reported that Necl-5 enhances cell proliferation by enhancement of Serum- and Platelet-derived Growth Factor through the Ras-Raf-MEK-ERK signaling. We investigated the function of CD155 about the cell proliferation and its signaling pathways to elucidate the role of CD155 in the cells. The CD155 cDNA or CD155- Δ CP cDNA (cytoplasmic deletion mutant of CD155 which works as a dominant negative of CD155) inserted in pCAGIPuro plasmids were induced to NIH3T3 (mouse fibroblast) cells, V12Ras-NIH3T3 (mouse fibroblast cells transfected with ras mutant gene) cells, and DLD-1 (human colon cancer) cells, respectively, establishing the cells stably expressing CD155 or CD155-ΔCP. The cells transfected only with pCAGIPuro plasmids were also established as control cells. The serum sensitivity to cell proliferation and cell growth were examined by counting the cells with Coulter Counter after 4-day incubation in DMEM supplemented with each density of FBS and after each days incubated with 7% FBS in DMEM. And the phases of the cell cycle were also examined by using fluorescence-activated cell sorter (FACS) after stimulation with 7% FBS in DMEM for 9 or 16 hours. Compared with control cells, the serum sensitivity and cell growth rate of NIH3T3/CD155 cells were decreased, but those of V12Ras-NIH3T3/CD155 cells were increased. And the serum sensitivity of V12Ras-NIH3T3/CD155-ΔCP cells was less enhanced compared with that of V12Ras-NIH3T3/CD155 cells. No significant change of serum sensitivity of DLD-1/CD155 cells, endogenously expressing CD155 and having K- ras gene-mutation, was seen compared with that of control cells. But in DLD-1/CD155-ΔCP cells, the serum sensitivity was decreased compared with those of control cells and DLD-1/CD155-ΔCP cells. This is assumed to be due to inhibition of endogenous CD155 by CD155-ΔCP. In FACS analysis, the shortening of the period of G0/G1 phase was seen in V12Ras-NIH3T3/CD155 cells compared with that of control cells. These results indicate that CD155 enhances the cell proliferation by shortening the period of G0/G1 phase in Ras gene-mutant cells.