Reprogrammed Schwann Cells Organize into Dynamic Tracks that Promote Pancreatic Cancer Invasion.
Reprogrammed Schwann Cells Organize into Dynamic Tracks that Promote Pancreatic Cancer Invasion.
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DOI：
10.1158/2159-8290.cd-21-1690
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发表时间：
2022-10-05
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影响因子：
28.2
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中科院分区：
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许旺细胞在胰腺癌中经历c-jun介导的重编程，类似于它们在创伤后的转分化，并共同组织成促进癌细胞侵袭的动态轨迹。神经是肿瘤微环境的组成部分，有助于癌症的进展，但神经细胞在促进癌症侵袭中的作用仍然知之甚少。在这里，我们展示了由癌细胞激活的雪旺细胞(SC)作为肿瘤激活的雪旺细胞轨迹(TAST)的共同功能，促进了癌细胞的迁移和侵袭。非髓鞘干细胞形成TAST，并具有与胰腺导管腺癌患者生存率降低相关的细胞基因表达特征。在TAST中，动态的SCs形成轨迹，作为癌症途径，并对癌细胞施加力量，以增强癌症的运动性。这些干细胞被c-jun激活，类似于它们在神经修复过程中的重新编程。这项研究揭示了一种癌细胞入侵的机制，它结合了伤口修复过程，并利用干细胞集体组织成轨道的能力。这些发现建立了癌细胞如何扩散的新范式，并揭示了治疗机会。肿瘤微环境如何参与胰腺癌的进展尚不完全清楚。在这里，我们展示了干细胞被癌细胞激活，并集体组织成轨道，以c-jun依赖的方式动态地使癌症侵袭。见Amit和Maitra的相关评论，第2240页。本文在本期特写中重点介绍，第2221页
Schwann cells undergo c-Jun–mediated reprogramming in pancreatic cancer, analogous to their trans-differentiation following trauma, and collectively organize into dynamic tracks that promote cancer cell invasion. Nerves are a component of the tumor microenvironment contributing to cancer progression, but the role of cells from nerves in facilitating cancer invasion remains poorly understood. Here we show that Schwann cells (SC) activated by cancer cells collectively function as tumor-activated Schwann cell tracks (TAST) that promote cancer cell migration and invasion. Nonmyelinating SCs form TASTs and have cell gene expression signatures that correlate with diminished survival in patients with pancreatic ductal adenocarcinoma. In TASTs, dynamic SCs form tracks that serve as cancer pathways and apply forces on cancer cells to enhance cancer motility. These SCs are activated by c-Jun, analogous to their reprogramming during nerve repair. This study reveals a mechanism of cancer cell invasion that co-opts a wound repair process and exploits the ability of SCs to collectively organize into tracks. These findings establish a novel paradigm of how cancer cells spread and reveal therapeutic opportunities. How the tumor microenvironment participates in pancreatic cancer progression is not fully understood. Here, we show that SCs are activated by cancer cells and collectively organize into tracks that dynamically enable cancer invasion in a c-Jun–dependent manner. See related commentary by Amit and Maitra, p. 2240. This article is highlighted in the In This Issue feature, p. 2221