Mechanism responsible for the antitumor effect of BCG-CWS using the LEEL method in a mouse bladder cancer model
Mechanism responsible for the antitumor effect of BCG-CWS using the LEEL method in a mouse bladder cancer model
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DOI：
10.1016/j.jconrel.2014.10.007
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发表时间：
2014-12-28
影响因子：
10.8
通讯作者：
Harashima, Hideyoshi
中科院分区：
文献类型：
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作者：
Nakamura, Takashi;Fukiage, Masafumi;Harashima, Hideyoshi
我们以前报道了通过将其封装到纳米颗粒（CWS-NP）中的BCG（BCG-CWS）的细胞壁骨架（BCG-CWS）（BCG-CWS）的开发。 CWS-NP使我们能够阐明与BCG介导的抗膀胱肿瘤效应相关的机械，尤其是膀胱癌细胞和树突状细胞（DC）的作用，在最初的一步中，这仍然很少理解。我们在这里表明，膀胱癌细胞（而非DC）对BCG-CW的内在化是必不可少的，这对于诱导针对膀胱癌的抗肿瘤作用是必不可少的。在接种含有内部BCG-CWS的小鼠膀胱癌（MBT-2）细胞的小鼠中，肿瘤生长显着抑制。另一方面，DC对BCG-CW的内在化仅对诱导针对MBT-2肿瘤的抗肿瘤作用的影响很小。通过使用CWS-NP首次澄清这一点。这一发现提供了我们对膀胱癌细胞和DC在针对膀胱癌中BCG治疗中的作用的了解。 （c）2014 Elsevier B.V.保留所有权利。
We previously reported on the development of a water soluble formulation of the cell wall skeleton of BCG (BCG-CWS), a major immune active center of BCG, by encapsulating it into a nanoparticle (CWS-NP). The CWS-NP allowed us to clarify the machinery associated with the BCG mediated anti-bladder tumor effect, especially the roles of bladder cancer cells and dendritic cells (DCs) in the initial step, which remains poorly understood. We show herein that the internalization of BCG-CWS by bladder cancer cells, but not DCs, is indispensable for the induction of an antitumor effect against bladder cancer. Tumor growth was significantly inhibited in mice that had been inoculated with mouse bladder cancer (MBT-2) cells containing internalized BCG-CWS. On the other hand, the internalization of BCG-CWS by DCs had only a minor effect on inducing an antitumor effect against MBT-2 tumors. This was clarified for the first time by using the CWS-NP. This finding provides insights into our understanding of the role of bladder cancer cells and DCs in BCG therapy against bladder cancer. (C) 2014 Elsevier B.V. All rights reserved.