Fas-negative @entity421 cells are selected during metastasis to the lungs: the role of the Fas pathway in the metastatic process of XXXX .

@entity1 @entity3478 @entity5 @entity19 @entity421 @entity358 @entity3 @entity9699 @entity51424
Low expression of Fas by different @entity5 including @entity421 , correlates with poor prognosis. We found that @entity358 @entity3 from @entity1 expressed negligible amounts of Fas, but primary @entity5 often expressed high Fas levels. The reason for this discrepancy is unknown. We hypothesized that because @entity9699 is constitutively expressed in the lungs, Fas-positive (Fas(+)) @entity5 cells entering the lungs would bind with @entity9699 and die from Fas-induced apoptosis, resulting in the "selection" of Fas-negative (Fas(-)) cells, which would eventually form @entity3 . To test this hypothesis, we injected @entity421 cells, which express functional Fas in vitro, into @entity19 and confirmed that its @entity3478 were Fas(+), but lung @entity3 were Fas(-). Next, to inhibit Fas signaling without affecting Fas expression, we transfected these cells with a @entity51424 -dominant negative (FDN) plasmid and developed K7/FDN cells. @entity3 formed by K7/FDN cells contained Fas(+) @entity5 cells. Moreover, K7/FDN cells were retained in the lungs longer and formed more lung @entity3 than K7 cells. In addition, the incidence of lung @entity3 in @entity9699 -deficient @entity19 injected with K7 cells was higher than that in wild-type @entity19 . @entity3 from @entity9699 -deficient @entity19 but not from wild-type @entity19 contained Fas(+) @entity5 cells. Based on that, we conclude that Fas(-) @entity421 cells are selected during lung @entity3 formation and that inhibition of Fas signaling in @entity5 or lack of @entity9699 in the host environment allows the proliferation of Fas(+) @entity421 cells in the lungs and promotes @entity3 growth. Therefore, Fas may be considered as a new therapeutic target for @entity421 treatment.
