Platelet activation supports tumor cell survival in the lungs via a mechanism coupled to NK cell function. (A) Quantitative analysis of residual radiolabeled LLCGFP cells within the lungs following intravenous injection. The values plotted are the percentage of the total tumor cells originally injected that were found within the lungs at the given time point (the data plotted are the mean values and standard deviations using cohorts of 5-6 mice). Note that the absence of Gαq had no effect on the initial localization of tumor cells in the lungs but resulted in a significant diminution in tumor cell survival when analyzed after either 5 (P < .03) or 24 hours (P < .01). (B) Loss of NK cell–mediated target cell lysis in vitro (standard chromium-release assays) by mononuclear splenocytes prepared from mice depleted of NK cells using an anti–asialo GM1 antibody. Shown are representative results using splenocytes from carrier treated (•) and anti–asialo GM1 antibody-treated mice (○). Note that anti–asialo GM1 effectively eliminated NK cell lysis of YAC-1 target cells even at the highest effector-to-target cell ratio tested. (C-D) Quantitative analysis of residual radiolabeled LLCGFP cells within the lung tissue 24 hours after intravenous injection into mice that were pretreated with anti–asialo GM1 to deplete NK cells (D) or pretreated in parallel with antibody carrier (C). Note that in control (carrier-treated) mice (C), Gαq was affirmed to be an important determinant of tumor cell fate; Gαq–/– mice (n = 6) had significantly fewer pulmonary tumor cells than control animals (n = 6) 24 hours after tumor cell inoculation (P < .01). However, in mice depleted of NK cells (D), no significant diminution in lung-associated tumor cells was observed in Gαq–/– mice (n = 5) relative to control animals (n = 8). All P values were generated using a Mann-Whitney U test. Error bars represent standard deviation.
