Cancer-Associated Neurogenesis and Nerve-Cancer Cross-talk.
Cancer-Associated Neurogenesis and Nerve-Cancer Cross-talk.
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DOI：
10.1158/0008-5472.can-20-2793
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发表时间：
2021-03-15
期刊：
影响因子：
11.2
通讯作者：
Amit M
中科院分区：
文献类型：
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作者：
Silverman DA;Martinez VK;Dougherty PM;Myers JN;Calin GA;Amit M
在这篇综述中，我们强调了最近的发现，有关机制有助于神经癌串扰和神经癌串扰对肿瘤进展和传播的影响。高肿瘤内神经密度与多种实体瘤类型的预后差和复发率高相关。最近的研究表明，癌细胞表达神经营养标志物，如神经生长因子，脑源性神经营养因子和胶质细胞源性神经营养因子，并释放轴突导向分子，如Ephrin B1，以促进轴突生成。肿瘤细胞募集新的神经祖细胞到肿瘤环境中，并促进它们成熟为肾上腺素能浸润神经。肿瘤还通过p53缺陷型肿瘤的外泌体诱导的神经重编程将已建立的神经重新连接到肾上腺素能表型。反过来，浸润的交感神经促进癌症进展。肿瘤内肾上腺素能神经通过血管内皮生长因子信号传导释放去甲肾上腺素以刺激血管生成并提高肿瘤生长速率。肿瘤内副交感神经可能在癌症进展中具有二分作用，并且可能诱导扩增癌症干细胞的Wnt-β-连环蛋白信号。重要的是，浸润神经不仅影响肿瘤细胞本身，而且影响肿瘤基质的其他细胞。这导致增强的交感神经信号传导和糖皮质激素产生，其影响中性粒细胞和巨噬细胞分化、淋巴细胞表型和潜在的淋巴细胞功能。虽然在这一领域仍有许多未探索的，但基本发现强调了神经-癌症串扰对肿瘤进展的重要性，并可能为开发抑制肿瘤诱导的神经发生和肿瘤进展的有效靶点提供基础。
In this review, we highlight recent discoveries regarding mechanisms contributing to nerve-cancer crosstalk and the effects of nerve-cancer crosstalk on tumor progression and dissemination. High intratumoral nerve density correlates with poor prognosis and high recurrence across multiple solid tumor types. Recent research has shown that cancer cells express neurotrophic markers such as nerve growth factor, brain-derived neurotrophic factor, and glial cell-derived neurotrophic factor and release axon guidance molecules such as Ephrin B1 to promote axonogenesis. Tumor cells recruit new neural progenitors to the tumor milieu and facilitate their maturation into adrenergic infiltrating nerves. Tumors also rewire established nerves to adrenergic phenotypes via exosome-induced neural reprogramming by p53-deficient tumors. In turn, infiltrating sympathetic nerves facilitate cancer progression. Intratumoral adrenergic nerves release noradrenaline to stimulate angiogenesis via vascular endothelial growth factor signaling and enhance the rate of tumor growth. Intratumoral parasympathetic nerves may have a dichotomous role in cancer progression and may induce Wnt-β-catenin signals that expand cancer stem cells. Importantly, infiltrating nerves not only influence the tumor cells themselves but also impact other cells of the tumor stroma. This leads to enhanced sympathetic signaling and glucocorticoid production, which influences neutrophil and macrophage differentiation, lymphocyte phenotype, and potentially lymphocyte function. Although much remains unexplored within this field, fundamental discoveries underscore the importance of nerve-cancer crosstalk to tumor progression and may provide the foundation for developing effective targets for the inhibition of tumor-induced neurogenesis and tumor progression.