Disabling partners in crime: Gold nanoparticles disrupt multicellular communications within the tumor microenvironment to inhibit ovarian tumor aggressiveness.
Disabling partners in crime: Gold nanoparticles disrupt multicellular communications within the tumor microenvironment to inhibit ovarian tumor aggressiveness.
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DOI：
10.1016/j.mattod.2022.01.025
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发表时间：
2022-06
期刊：
影响因子：
24.2
通讯作者：
Mukherjee, Priyabrata
中科院分区：
文献类型：
--
作者：
Zhang, Yushan;Elechalawar, Chandra Kumar;Yang, Wen;Frickenstein, Alex N.;Asfa, Sima;Fung, Kar-Ming;Murphy, Brennah N.;Dwivedi, Shailendra K.;Rao, Geeta;Dey, Anindya;Wilhelm, Stefan;Bhattacharya, Resham;Mukherjee, Priyabrata
关键词：
肿瘤微环境（TME）在许多癌症的不良预后中起着关键作用。然而，关于TME中关键参与者之间的多细胞通信如何导致这种不良结果，存在知识差距。使用上皮性卵巢癌（EOC）作为模型，我们展示了癌细胞（CC），癌相关成纤维细胞（CAF）和内皮细胞（EC）之间的串扰如何促进EOC生长。我们在这里证明，CC与CAF和EC的共培养促进CC增殖，迁移和体外侵袭，并且三种细胞类型的共植入促进体内肿瘤生长。我们进一步证明了使用金纳米颗粒（GNP）破坏这种多细胞串扰在体外抑制这些促肿瘤发生表型以及在体内抑制肿瘤生长。从机制上讲，GNP治疗降低了几种促肿瘤细胞因子和生长因子的表达，导致MAPK和PI 3 K-AKT活化和上皮-间质转化的抑制-这是导致EOC侵袭性的三种关键致癌信号传导途径。目前的工作突出了TME内多细胞串扰的重要性及其对EOC侵袭性的作用，并证明了自我治疗性GNP对这些多细胞通信的破坏，从而提供了新的途径来询问串扰并确定导致这种难治性恶性肿瘤预后不良的关键肇事者。
The tumor microenvironment (TME) plays a key role in the poor prognosis of many cancers. However, there is a knowledge gap concerning how multicellular communication among the critical players within the TME contributes to such poor outcomes. Using epithelial ovarian cancer (EOC) as a model, we show how crosstalk among cancer cells (CC), cancer associated fibroblasts (CAF), and endothelial cells (EC) promotes EOC growth. We demonstrate here that co-culturing CC with CAF and EC promotes CC proliferation, migration, and invasion in vitro and that co-implantation of the three cell types facilitates tumor growth in vivo. We further demonstrate that disruption of this multicellular crosstalk using a gold nanoparticle (GNP) inhibits these pro-tumorigenic phenotypes in vitro as well as tumor growth in vivo. Mechanistically, GNP treatment reduces expression of several tumor-promoting cytokines and growth factors, resulting in inhibition of MAPK and PI3K-AKT activation and epithelial-mesenchymal transition - three key oncogenic signaling pathways responsible for the aggressiveness of EOC. The current work highlights the importance of multicellular crosstalk within the TME and its role for the aggressive nature of EOC, and demonstrates the disruption of these multicellular communications by self-therapeutic GNP, thus providing new avenues to interrogate the crosstalk and identify key perpetrators responsible for poor prognosis of this intractable malignancy.
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影响因子：
7.3
作者：
Gonzalez DM;Medici D
通讯作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.1214547110
发表时间：
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影响因子：
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