Heat shock protein DNAJB8 is a novel target for immunotherapy of colon cancer-initiating cells.
Heat shock protein DNAJB8 is a novel target for immunotherapy of colon cancer-initiating cells.
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DOI：
10.1111/cas.12362
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发表时间：
2014-04
期刊：
影响因子：
5.7
通讯作者：
Sato N
中科院分区：
文献类型：
--
作者：
Morita R;Nishizawa S;Torigoe T;Takahashi A;Tamura Y;Tsukahara T;Kanaseki T;Sokolovskaya A;Kochin V;Kondo T;Hashino S;Asaka M;Hara I;Hirohashi Y;Sato N
本研究的目的是建立肿瘤干细胞/癌起始细胞（CSC/CIC）靶向免疫疗法。CSC/CIC被认为对肿瘤维持、复发和远处转移至关重要。因此它们是癌症治疗的合理靶点。在本研究中，我们发现热休克蛋白（HSP） 40家族成员，DnaJ （Hsp40）同系物，B亚家族成员8 (DNAJB8)，优先表达来自结直肠癌（CRC）细胞的CSC/CIC而不是非CSC/CIC。过表达DNAJB8可增强干细胞标志物的表达和致瘤性，提示DNAJB8在CRC CSC/CIC中发挥作用。dnajb8衍生的抗原肽可诱导dnajb8特异性细胞毒性T淋巴细胞（CTL）反应。DNAJB8肽特异性CTL克隆对CRC CSC/CIC的杀伤活性高于非CSC/CIC， CTL过继转入CRC CSC/CIC具有体内抗肿瘤作用。综上所述，DNAJB8在CRC CSC/CIC中表达并发挥作用，DNAJB8是CRC CSC/CIC靶向免疫治疗的新靶点。
The aim of the present study was to establish cancer stem-like cell/cancer-initiating cell (CSC/CIC)-targeting immunotherapy. The CSC/CIC are thought to be essential for tumor maintenance, recurrence and distant metastasis. Therefore they are reasonable targets for cancer therapy. In the present study, we found that a heat shock protein (HSP) 40 family member, DnaJ (Hsp40) homolog, subfamily B, member 8 (DNAJB8), is preferentially expressed in CSC/CIC derived from colorectal cancer (CRC) cells rather than in non-CSC/CIC. Overexpression of DNAJB8 enhanced the expression of stem cell markers and tumorigenicity, indicating that DNAJB8 has a role in CRC CSC/CIC. A DNAJB8-specific cytotoxic T lymphocyte (CTL) response could be induced by a DNAJB8-derived antigenic peptide. A CTL clone specific for DNAJB8 peptide showed higher killing activity to CRC CSC/CIC compared with non-CSC/CIC, and CTL adoptive transfer into CRC CSC/CIC showed an antitumor effect in vivo. Taken together, the results indicate that DNAJB8 is expressed and has role in CRC CSC/CIC and that DNAJB8 is a novel target of CRC CSC/CIC-targeting immunotherapy.
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影响因子：
7.4
作者：
Tsuruma T;Iwayama Y;Ohmura T;Katsuramaki T;Hata F;Furuhata T;Yamaguchi K;Kimura Y;Torigoe T;Toyota N;Yagihashi A;Hirohashi Y;Asanuma H;Shimozawa K;Okazaki M;Mizushima Y;Nomura N;Sato N;Hirata K
通讯作者：
Hirata K
影响因子：
11.2
作者：
Huang EH;Hynes MJ;Zhang T;Ginestier C;Dontu G;Appelman H;Fields JZ;Wicha MS;Boman BM
通讯作者：
Boman BM
影响因子：
7.2
作者：
Hirohashi Y;Torigoe T;Inoda S;Morita R;Kochin V;Sato N
通讯作者：
Sato N
影响因子：
64.8
作者：
Greaves, Mel;Maley, Carlo C.
通讯作者：
Maley, Carlo C.
影响因子：
7.3
作者：
Burkert, J.;Otto, W. R.;Wright, N. A.
通讯作者：
Wright, N. A.