Interrupting Neuron-Tumor Interactions to Overcome Treatment Resistance.
Interrupting Neuron-Tumor Interactions to Overcome Treatment Resistance.
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DOI：
10.3390/cancers12123741
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发表时间：
2020-12-12
期刊：
影响因子：
5.2
通讯作者：
Amit M
中科院分区：
文献类型：
--
作者：
Hunt PJ;Kabotyanski KE;Calin GA;Xie T;Myers JN;Amit M
实体癌利用周围组织刺激自身生长，促进其扩散，并逃避抗癌免疫反应和治疗。神经元是一个重要的新发现的肿瘤靶点，因为它们可以提供所有这些好处，并在整个身体中发现。神经元使用化学信号进行通信，其中许多可以被肿瘤细胞识别和利用。反过来，肿瘤通过发送驱动神经元生长到肿瘤体内的局部信号来操纵神经元。与局部信号传导相结合，肿瘤在细胞外囊泡内传递蛋白质和RNA信使，这些囊泡通过血流和其他体液传播。这种长距离肿瘤信号传导是一个不断发展的研究领域，它允许新的诊断和治疗方法。正在进行的临床试验将揭示破坏肿瘤-神经元通信的方法，以造福患者。肿瘤微环境中的神经元释放神经递质、神经胶质素、趋化因子、可溶性生长因子和膜结合生长因子，实体瘤利用这些因子来驱动其自身的存活和扩散。肿瘤表达支持局部神经元并引导神经元生长到肿瘤中的神经特异性生长因子和microRNA。肿瘤和神经元之间前馈关系的发展允许肿瘤使用神经周围空间作为治疗的避难所。在动物模型中，肿瘤去神经支配减慢肿瘤生长，证明了生长肿瘤的神经支配依赖性。进一步的体外和体内实验已经鉴定了许多分泌的信号分子（例如，乙酰胆碱，神经生长因子），以及主要的信号传导途径（例如，MAPK/EGFR）参与这些营养相互作用。参与这些信号通路的分子可作为疾病的潜在生物标志物。此外，新的治疗策略侧重于使用小分子、受体激动剂、神经特异性毒素和外科手术干预来靶向肿瘤、神经元和肿瘤微环境的免疫细胞，从而切断肿瘤与周围神经元之间的相互作用。本文讨论了神经元和肿瘤之间形成的营养关系的机制，并探讨了这项工作产生的新兴疗法。
Solid cancers take advantage of the surrounding tissue to stimulate their own growth, to promote their spread, and to escape anticancer immune responses and treatments. Neurons are an important newly identified target for tumors because they can provide all of these benefits and are found throughout the body. Neurons communicate using chemical signals, many of which can be recognized and leveraged by tumor cells. Tumors, in turn, manipulate neurons by sending local signals that drive the growth of neurons into the body of the tumor. In tandem with local signaling, tumors transmit protein and RNA messengers within extracellular vesicles that travel through the bloodstream and other bodily fluids. This long-range tumor signaling is a growing area of research that allows for new diagnostic and therapeutic approaches. Ongoing clinical trials will uncover methods of disrupting tumor–neuron communication for the benefit of patients. Neurons in the tumor microenvironment release neurotransmitters, neuroligins, chemokines, soluble growth factors, and membrane-bound growth factors that solid tumors leverage to drive their own survival and spread. Tumors express nerve-specific growth factors and microRNAs that support local neurons and guide neuronal growth into tumors. The development of feed-forward relationships between tumors and neurons allows tumors to use the perineural space as a sanctuary from therapy. Tumor denervation slows tumor growth in animal models, demonstrating the innervation dependence of growing tumors. Further in vitro and in vivo experiments have identified many of the secreted signaling molecules (e.g., acetylcholine, nerve growth factor) that are passed between neurons and cancer cells, as well as the major signaling pathways (e.g., MAPK/EGFR) involved in these trophic interactions. The molecules involved in these signaling pathways serve as potential biomarkers of disease. Additionally, new treatment strategies focus on using small molecules, receptor agonists, nerve-specific toxins, and surgical interventions to target tumors, neurons, and immune cells of the tumor microenvironment, thereby severing the interactions between tumors and surrounding neurons. This article discusses the mechanisms underlying the trophic relationships formed between neurons and tumors and explores the emerging therapies stemming from this work.
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DOI：
10.1002/pros.23454
发表时间：
2018-03
期刊：
The Prostate
影响因子：
--
作者：
Coarfa C;Florentin D;Putluri N;Ding Y;Au J;He D;Ragheb A;Frolov A;Michailidis G;Lee M;Kadmon D;Miles B;Smith C;Ittmann M;Rowley D;Sreekumar A;Creighton CJ;Ayala G
通讯作者：
Ayala G
影响因子：
21.3
作者：
Costa-Silva B;Aiello NM;Ocean AJ;Singh S;Zhang H;Thakur BK;Becker A;Hoshino A;Mark MT;Molina H;Xiang J;Zhang T;Theilen TM;García-Santos G;Williams C;Ararso Y;Huang Y;Rodrigues G;Shen TL;Labori KJ;Lothe IM;Kure EH;Hernandez J;Doussot A;Ebbesen SH;Grandgenett PM;Hollingsworth MA;Jain M;Mallya K;Batra SK;Jarnagin WR;Schwartz RE;Matei I;Peinado H;Stanger BZ;Bromberg J;Lyden D
通讯作者：
Lyden D
STAT3信号通路诱导的BDNF自分泌活性导致TrkB延长激活并促进人非小细胞肺癌增殖
影响因子：
4.6
作者：
Chen B;Liang Y;He Z;An Y;Zhao W;Wu J
通讯作者：
Wu J
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
11.2
作者：
Allen JK;Armaiz-Pena GN;Nagaraja AS;Sadaoui NC;Ortiz T;Dood R;Ozcan M;Herder DM;Haemmerle M;Gharpure KM;Rupaimoole R;Previs RA;Wu SY;Pradeep S;Xu X;Han HD;Zand B;Dalton HJ;Taylor M;Hu W;Bottsford-Miller J;Moreno-Smith M;Kang Y;Mangala LS;Rodriguez-Aguayo C;Sehgal V;Spaeth EL;Ram PT;Wong STC;Marini FC;Lopez-Berestein G;Cole SW;Lutgendorf SK;De Biasi M;Sood AK
通讯作者：
Sood AK