BACKGROUND Although accumulating evidence suggests that the crosstalk between malignant cells and cancer-associated fibroblasts (CAFs) actively contributes to tumour growth and metastatic dissemination, therapeutic strategies targeting tumour stroma are still not common in the clinical practice. Metal-based nanomaterials have been shown to exert excellent cytotoxic and anti-cancerous activities, however, their effects on the reactive stroma have never been investigated in details. Thus, using feasible in vitro and in vivo systems to model tumour microenvironment, we tested whether the presence of gold, silver or gold-core silver-shell nanoparticles exerts anti-tumour and metastasis suppressing activities by influencing the tumour-supporting activity of stromal fibroblasts. RESULTS We found that the presence of gold-core silver-shell hybrid nanomaterials in the tumour microenvironment attenuated the tumour cell-promoting behaviour of CAFs, and this phenomenon led to a prominent attenuation of metastatic dissemination in vivo as well. Mechanistically, transcriptome analysis on tumour-promoting CAFs revealed that silver-based nanomaterials trigger expressional changes in genes related to cancer invasion and tumour metastasis. CONCLUSIONS Here we report that metal nanoparticles can influence the cancer-promoting activity of tumour stroma by affecting the gene expressional and secretory profiles of stromal fibroblasts and thereby altering their intrinsic crosstalk with malignant cells. This potential of metal nanomaterials should be exploited in multimodal treatment approaches and translated into improved therapeutic outcomes.

中文翻译：

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核壳纳米粒子可抑制转移并改变与癌症相关的成纤维细胞的肿瘤支持活性。

背景技术尽管有越来越多的证据表明，恶性细胞与癌症相关的成纤维细胞（CAF）之间的串扰积极地促进了肿瘤的生长和转移性扩散，但在临床实践中，针对肿瘤基质的治疗策略仍然并不普遍。金属基纳米材料已显示出优异的细胞毒性和抗癌活性，但是，它们对反应性基质的作用尚未得到详细研究。因此，我们使用可行的体外和体内系统对肿瘤微环境进行建模，我们测试了金，银或金核银壳纳米颗粒的存在是否通过影响基质成纤维细胞的肿瘤支持活性而发挥抗肿瘤和转移抑制活性。结果我们发现，在肿瘤微环境中金芯银壳杂化纳米材料的存在减弱了CAFs促进肿瘤细胞的行为，并且这种现象也导致体内转移扩散的显着减弱。从机理上讲，对促进肿瘤的CAF进行转录组分析发现，基于银的纳米材料触发了与癌症侵袭和肿瘤转移相关的基因的表达变化。结论在这里我们报道金属纳米粒子可以通过影响基质成纤维细胞的基因表达和分泌特性，从而改变其与恶性细胞的内在干扰，来影响肿瘤基质的促癌活性。