CR
cDNA was transfected into murine T-Ag-
MOSE ovarian cancer cells by lipofection. CR-transfected cells (CR induction group) or empty vector-treated cells (control group) were injected into the backs of 8-week-old nude mice at a concentration of 0.5 × 10(6) per 0.2 mL. Subsequent
tumor proliferation in both groups was observed for 5 weeks.
RESULTS: The control group showed an increase in
tumor volume during the 5 weeks of observation. However,
tumor volume in the CR induction group increased up to the second week but then decreased continuously until the fifth week of observation. The
tumor growth curves for the two groups showed a significant difference (Mann-Whitney U test, P < 0.001). Histological and biochemical experiments were performed using
tumor tissues isolated in the third week.
Necrosis and inflammatory cell infiltration were noted for
tumors in the CR induction group. Also, the number of apoptotic cells was significantly increased in the CR induction group compared with the control group (P < 0.001).
Milk fat globule EGF factor 8, an "eat-me" signal for phagocytes such as macrophages, was expressed extensively in the
tumor cytoplasm and interstitial cells of the CR induction group, and engulfment of apoptotic cells by macrophages was observed.
Vascular endothelial growth factor expression in
tumors was notably decreased in the CR induction group compared with the control group.
CONCLUSION: Increased
necrosis due to engulfing of apoptotic cells by phagocytes attracted by increased
milk fat globule EGF factor 8 was considered to be the mechanism of spontaneous
tumor regression in the CR induction group.