Selective neutralization of IL-12 p40 monomer induces death in prostate cancer cells via IL-12-IFN-γ
Selective neutralization of IL-12 p40 monomer induces death in prostate cancer cells via IL-12-IFN-γ
复制标题
选择性中和IL-12 p40单体通过IL-12-IFN-γ诱导前列腺癌细胞死亡
DOI：
10.1073/pnas.1705536114
复制
发表时间：
2017-10-24
影响因子：
11.1
通讯作者：
Pahan, Kalipada
中科院分区：
文献类型：
--
作者：
Kundu, Madhuchhanda;Roy, Avik;Pahan, Kalipada
Cancer cells are adept at evading cell death, but the underlying mechanisms are poorly understood. IL-12 plays a critical role in the early inflammatory response to infection and in the generation of T-helper type 1 cells, favoring cell-mediated immunity. IL-12 is composed of two different subunits, p40 and p35. This study underlines the importance of IL-12 p40 monomer (p40) in helping cancer cells to escape cell death. We found that different mouse and human cancer cells produced greater levels of p40 than p40 homodimer (p40(2)), IL-12, or IL-23. Similarly, the serum level of p40 was much greater in patients with prostate cancer than in healthy control subjects. Selective neutralization of p40, but not p40(2), by mAb stimulated death in different cancer cells in vitro and in vivo in a tumor model. Interestingly, p40 was involved in the arrest of IL-12 receptor (IL-12R) IL-12R beta 1, but not IL-12R beta 2, in the membrane, and that p40 neutralization induced the internalization of IL-12R beta 1 via caveolin and caused cancer cell death via the IL-12-IFN-gamma pathway. These studies identify a role of p40 monomer in helping cancer cells to escape cell death via suppression of IL-12R beta 1 internalization.
