Growth of FasL-bearing tumor cells in syngeneic murine host induces apoptosis and toxicity in Fas+ organs

In the current study, we investigated whether the growth of Fast-bearing tumor cells would induce apoptosis and toxicity in organs that express high level of Fas, Sera from C57BL/6 +/+ (wild-type) mice injected with syngeneic FasL(+) tumors, LSA, or EL-4, showed significantly higher levels of soluble Fast than that from the nontumor-bearing mice. Furthermore, the soluble Fast was functional inasmuch as the sera from tumor-bearing mice were able to induce apoptosis in Fas(+) but not Fas(-) targets. Histopathologic studies and in situ TUNEL assay to detect apoptosis were carried out in C57BL/6 +/+ (Fas(+)) or C57BL/6 Ipr/Ipr (Fas(-)) mice injected with syngeneic LSA and EL-4 tumor cells. The morphology of the liver and thymus from tumor bearing C57BL/6 +/+ mice showed marked damage and tissue destruction, In contrast, the liver and thymus from tumor-bearing C57BL/6 Ipr/Ipr mice showed minimal damage. Furthermore, the tumor-bearing C57BL/6 +/+, but not the C57BL/6 Ipr/Ipr, mice exhibited significant apoptosis in the liver and thymus, The Fast responsible for toxicity was tumor derived rather than host derived; tumor-bearing C57BL/6 gld/gld (FasL-defective) mice also exhibited significant apoptosis in the liver and thymus, Together, these data suggested that the in vivo growth of Fast-bearing tumor cells can induce significant apoptosis and toxicity in Fas(+) tissues of the host, Such toxicity may be mediated by the soluble Fast produced by tumor cells. (C) 2000 by The American Society of Hematology.