Inhibition of tumor progression by suppression of stress protein GRP78/BiP induction in fibrosarcoma B/C10ME

被引:231
|
作者
Jamora, C
Dennert, G
Lee, AS
机构
[1] UNIV SO CALIF,SCH MED,DEPT BIOCHEM & MOLEC BIOL,LOS ANGELES,CA 90033
[2] UNIV SO CALIF,SCH MED,DEPT MICROBIOL,LOS ANGELES,CA 90033
[3] UNIV SO CALIF,SCH MED,NORRIS CANC CTR,LOS ANGELES,CA 90033
关键词
D O I
10.1073/pnas.93.15.7690
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Stress protein GRP78/BiP is highly induced in progressively growing tumors acid has recently been shown to exert a protective role against lysis by cytotoxic T cells and tumor necrosis factor in vitro. This raises the question whether the in vitro observed protective function of GRP78/BiP translates into the in vivo situation in which tumors grow progressively , killing the host, Herein we report that molecular inhibition of GRP78/BiP induction in the fibrosarcoma B/C10ME, while not affecting in vitro cell proliferation, causes a dramatic increase in apoptotic cell death upon Ca2+ depletion of the endoplasmic reticulum. When B/C10ME cells incapable of inducing GRP78/BiP are injected into mice, tumors are initially formed that, however, regress presumably due to a cytotoxic T-cell response demonstrable by a strong in vitro response to the tumor with spleen cells of regressor mice, Since sensitivity to apoptosis is key to tumor rejection, these results may point to new approaches to the therapy of cancer via regulation of stress protein GRP78/BiP.
引用
收藏
页码:7690 / 7694
页数:5
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