Tumor metastasis is abrogated in Asm-deficient mice and restored by transplantation of wild-type platelets
A, B 1 × 105 B16F10 melanoma cells were intravenously injected into C57BL/6 wild-type (WT) or Asm-deficient (Asm−/−) mice, and the number of lung metastases was determined after 14 days. The photographs (A) show two representative results. The graph (B) shows the mean ± SD number of pulmonary metastases in 15 WT and 14 Asm-deficient animals.
C, D B16F10 melanoma grow as fast or slightly faster in Asm-deficient mice than in wild-type mice after subcutaneous injection at the flank (C) or transcutaneous direct intrapulmonary injection (D), excluding a general growth defect of the tumor in Asm-deficient mice. The size of tumors was determined 14 days after local injection at the flank or 10 days after injection into the lung.
E The number of lung metastases 25 days after intravenous injection does not differ from the number observed after 14 days in (B).
F 5 × 108 platelets isolated from wild-type (WT) or Asm-deficient (Asm−/−) mice were injected intravenously into Asm-deficient or wild-type mice, respectively. After 120 min 1 × 105, B16F10 tumor cells were intravenously injected. The number of lung metastases was determined after 14 days. Displayed are the mean ± SD of the number of pulmonary metastases, n = 3 in WT platelets in WT mice, n = 5 in WT platelets in Asm−/− mice, and n = 4 in Asm−/− platelets in Asm−/− mice.
Data information: Shown is the mean ± SD,
n = 5 (C–E). Statistical significance was determined by
t-test for single comparisons or analysis of variance (ANOVA) followed by a Tukey's multiple comparisons test.
P-values are given.