Reprogramming of cancer invasiveness and macrophage education via a nanostructured antagonist of the TGFβ receptor
Reprogramming of cancer invasiveness and macrophage education via a nanostructured antagonist of the TGFβ receptor
复制标题
通过 TGF β 受体纳米结构拮抗剂重新编程癌症侵袭性和巨噬细胞教育
DOI：
10.1039/c9mh00388f
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发表时间：
2019-10-01
影响因子：
13.3
通讯作者：
Song, Haiyun
中科院分区：
文献类型：
--
作者：
Liu, Chang;Hu, Xingjie;Song, Haiyun
纳米颗粒（NPs）在进入生命系统后可以与多种内源性蛋白质相互作用。然而，NP吸附对蛋白质功能和随后的细胞行为的影响知之甚少。在这里，应用质谱分析来描绘癌细胞中纳米金刚石（ND）相互作用组网络的蛋白质组规模图，其将转化生长因子β（TGF β）II型受体（T β RII）鉴定为高亲和力结合伴侣。进一步的研究表明，ND促进T β RII的溶酶体降解，从而通过阻断TGF β信号级联抑制培养的癌细胞、肿瘤类器官和异种移植肿瘤的侵袭和转移。值得注意的是，ND的静脉内施用减少了肿瘤相关巨噬细胞（TAM）的募集并抑制了肿瘤微环境中的M2巨噬细胞极化。因此，本研究揭示了NDs作为一种受体拮抗剂，并表明其在癌症治疗中的治疗作用。
Nanoparticles (NPs) can interact with a large variety of endogenous proteins upon entering a living system. However, the effects of NP adsorption on protein functions and consequent cellular behaviors are poorly understood. Here, a mass spectrometry analysis is applied to delineate a proteome-scale map of the nanodiamond (ND) interactome network in cancer cells, which identifies the transforming growth factor beta (TGF beta) type II receptor (T beta RII) as a high affinity binding partner. Further investigation shows that NDs promote the lysosomal degradation of T beta RII, and thereby suppress the invasion and metastasis of cultured cancer cells, tumor organoids and xenograft tumors via the blockade of the TGF beta signaling cascade. Significantly, intravenous administration of NDs reduces the recruitment of tumor-associated macrophages (TAMs) and inhibits M2 macrophage polarization in the tumor microenvironment. This study thus reveals NDs as a type of receptor antagonist and suggests their therapeutic effect in cancer treatment.