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Exosomal non-coding RNAs (ncRNAs) as potential biomarkers in tumor early diagnosis 外泌体非编码 RNA(ncRNA)作为肿瘤早期诊断的潜在生物标记物。
IF 9.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-21 DOI: 10.1016/j.bbcan.2024.189188
Exosomes, extracellular vesicles carrying a cargo rich in various non-coding RNAs (ncRNAs), have emerged as crucial mediators of intercellular communication. Their stability, abundance, and specificity make exosomal ncRNAs promising candidates for biomarker discovery. The discovery of exosomal ncRNAs has unveiled a novel avenue for the exploration of biomarkers in tumor early diagnosis. This review consolidates current knowledge on the role of exosomal ncRNAs as potential biomarkers in the early detection of various tumors. We provide an overview of recent studies demonstrating the diagnostic potential of exosomal ncRNAs across multiple cancer types, highlighting their sensitivity, specificity, and feasibility for early detection. This review underscores the potential of exosomal ncRNAs as non-invasive biomarkers for early tumor diagnosis, paving the way for improved clinical outcomes through timely intervention and personalized management strategies.
外泌体是一种细胞外囊泡,携带着富含各种非编码 RNA(ncRNA)的货物,已成为细胞间通信的重要媒介。外泌体 ncRNA 的稳定性、丰富性和特异性使其成为发现生物标记物的理想候选物。外泌体 ncRNA 的发现为探索肿瘤早期诊断的生物标志物开辟了一条新途径。本综述整合了目前关于外泌体 ncRNA 作为潜在生物标记物在各种肿瘤早期检测中的作用的知识。我们概述了证明外泌体 ncRNA 在多种癌症类型中的诊断潜力的最新研究,强调了它们在早期检测中的敏感性、特异性和可行性。这篇综述强调了外泌体 ncRNA 作为非侵入性生物标记物用于早期肿瘤诊断的潜力,为通过及时干预和个性化管理策略改善临床结果铺平了道路。
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引用次数: 0
Unraveling the mysteries of MGMT: Implications for neuroendocrine tumors 揭开 MGMT 的神秘面纱:对神经内分泌肿瘤的影响。
IF 9.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-18 DOI: 10.1016/j.bbcan.2024.189184
Neuroendocrine tumors (NETs) are a diverse group of tumors that arise from neuroendocrine cells and are commonly found in various organs. A considerable proportion of NET patients were diagnosed at an advanced or metastatic stage. Alkylating agents are the primary treatment for NET, and O6-methylguanine methyltransferase (MGMT) remains the first-line of defense against DNA damage caused by these agents. Clinical trials have indicated that MGMT promoter methylation or its low/lacked expression can predict a favorable outcome with Temozolomide in NETs. Its status could help select NET patients who can benefit from alkylating agents. Therefore, MGMT status serves as a biomarker to guide decisions on the efficacy of Temozolomide as a personalized treatment option. Additionally, delving into the regulatory mechanisms of MGMT status can lead to the development of MGMT-targeted therapies, benefiting individuals with high levels of MGMT expression. This review aims to explore the polymorphism of MGMT regulation and summarize its clinical implications in NETs, which would help establish the role of MGMT as a biomarker and its potential as a therapeutic target in NETs. Additionally, we explore the benefits of combining Temozolomide and immunotherapy in MGMT hypermethylated subgroups. Future studies can focus on optimizing Temozolomide administration to induce specific immunomodulatory changes.
神经内分泌肿瘤(NET)是一类由神经内分泌细胞引起的多种肿瘤,常见于各种器官。相当一部分NET患者被诊断为晚期或转移期。烷化剂是治疗 NET 的主要药物,而 O6-甲基鸟嘌呤甲基转移酶(MGMT)仍然是抵御这些药物造成的 DNA 损伤的第一道防线。临床试验表明,MGMT 启动子甲基化或其低/缺乏表达可预测替莫唑胺治疗 NET 的良好疗效。它的状态有助于筛选出能从烷化剂中获益的 NET 患者。因此,MGMT 状态可作为一种生物标志物,指导替莫唑胺作为一种个性化治疗方案的疗效决策。此外,深入研究 MGMT 状态的调控机制可以开发 MGMT 靶向疗法,使高水平 MGMT 表达的个体受益。本综述旨在探讨MGMT调控的多态性并总结其在NET中的临床意义,这将有助于确立MGMT作为生物标志物的作用及其作为NET治疗靶点的潜力。此外,我们还探讨了在MGMT高甲基化亚组中联合使用替莫唑胺和免疫疗法的益处。未来的研究可侧重于优化替莫唑胺的用药,以诱导特定的免疫调节变化。
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引用次数: 0
Biomechanical properties of laminins and their impact on cancer progression 层粘连蛋白的生物力学特性及其对癌症进展的影响
IF 9.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-18 DOI: 10.1016/j.bbcan.2024.189181

Laminins (LMs) constitute a family of heterotrimeric glycoproteins essential for the formation of basement membranes (BM). They act as molecular bridges between cells and the extracellular matrix (ECM), thereby transmitting signals influencing cell behavior and tissue organization. In the realm of cancer pathobiology, LMs regulate key processes such as migration, differentiation, or fibrosis. This review critically examines the multifaceted impact of LMs on tumor progression, with a particular focus on the isoform-specific structure-function relationships, and how this structural diversity contributes to the biomechanical properties of BMs. LM interactions with integrin and non-integrin cell surface receptors, as well as with other ECM proteins, modify the response of cancer cells to the ECM stiffness, ultimately influencing the capacity of malignant cells to breach the BM, a limiting step in metastatic dissemination. Comprehension of the mechanisms underlying LM-driven tumor biomechanics holds potential for better understand cancer pathobiology and design new targeted therapeutic strategies.

层粘连蛋白(LMs)是形成基底膜(BM)所必需的一种异源三聚糖蛋白。它们是细胞与细胞外基质(ECM)之间的分子桥梁,从而传递影响细胞行为和组织结构的信号。在癌症病理生物学领域,LMs 可调控迁移、分化或纤维化等关键过程。本综述批判性地研究了 LMs 对肿瘤进展的多方面影响,尤其关注同工酶特异性的结构-功能关系,以及这种结构多样性如何促进 BMs 的生物力学特性。LM 与整合素和非整合素细胞表面受体以及其他 ECM 蛋白的相互作用改变了癌细胞对 ECM 硬度的反应,最终影响了恶性细胞突破 BM 的能力,而这正是转移扩散的限制性步骤。了解 LM 驱动肿瘤生物力学的基本机制有助于更好地理解癌症病理生物学并设计新的靶向治疗策略。
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引用次数: 0
Pancreatic ductal adenocarcinoma cells reshape the immune microenvironment: Molecular mechanisms and therapeutic targets 胰腺导管腺癌细胞重塑免疫微环境:分子机制和治疗靶点
IF 9.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-18 DOI: 10.1016/j.bbcan.2024.189183

Pancreatic ductal adenocarcinoma (PDAC) is a digestive system malignancy characterized by challenging early detection, limited treatment alternatives, and generally poor prognosis. Although there have been significant advancements in immunotherapy for hematological malignancies and various solid tumors in recent decades, with impressive outcomes in recent preclinical and clinical trials, the effectiveness of these therapies in treating PDAC continues to be modest. The unique immunological microenvironment of PDAC, especially the abnormal distribution, complex composition, and variable activation states of tumor-infiltrating immune cells, greatly restricts the effectiveness of immunotherapy. Undoubtedly, integrating data from both preclinical models and human studies helps accelerate the identification of reliable molecules and pathways responsive to targeted biological therapies and immunotherapies, thereby continuously optimizing therapeutic combinations. In this review, we delve deeply into how PDAC cells regulate the immune microenvironment through complex signaling networks, affecting the quantity and functional status of immune cells to promote immune escape and tumor progression. Furthermore, we explore the multi-modal immunotherapeutic strategies currently under development, emphasizing the transformation of the immunosuppressive environment into an anti-tumor milieu by targeting specific molecular and cellular pathways, providing insights for the development of novel treatment strategies.

胰腺导管腺癌(PDAC)是一种消化系统恶性肿瘤,其特点是难以早期发现、治疗手段有限、预后普遍较差。尽管近几十年来血液恶性肿瘤和各种实体瘤的免疫疗法取得了重大进展,最近的临床前和临床试验也取得了令人瞩目的成果,但这些疗法在治疗 PDAC 方面的效果仍然不佳。PDAC 独特的免疫微环境,尤其是肿瘤浸润免疫细胞的异常分布、复杂组成和多变活化状态,极大地限制了免疫疗法的有效性。毫无疑问,整合临床前模型和人体研究的数据有助于加速鉴定对靶向生物疗法和免疫疗法有反应的可靠分子和通路,从而不断优化治疗组合。在这篇综述中,我们将深入探讨 PDAC 细胞如何通过复杂的信号网络调节免疫微环境,影响免疫细胞的数量和功能状态,从而促进免疫逃逸和肿瘤进展。此外,我们还探讨了目前正在开发的多模式免疫治疗策略,强调通过靶向特定的分子和细胞通路将免疫抑制环境转变为抗肿瘤环境,为新型治疗策略的开发提供启示。
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引用次数: 0
War or peace: Viruses and metastasis 战争还是和平病毒与转移
IF 9.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-17 DOI: 10.1016/j.bbcan.2024.189179

Metastasis, the dissemination of malignant cells from a primary tumor to secondary sites, poses a catastrophic burden to cancer treatment and is the predominant cause of mortality in cancer patients. Metastasis as one of the main aspects of cancer progression could be strongly under the influence of viral infections. In fact, viruses have been central to modern cancer research and are associated with a great number of cancer cases. Viral-encoded elements are involved in modulating essential pathways or specific targets that are implicated in different stages of metastasis. Considering the continuous emergence of new viruses and the establishment of their contribution to cancer progression, the warfare between viruses and cancer appears to be endless. Here we aimed to review the critical mechanism and pathways involved in cancer metastasis and the influence of viral machinery and various routes that viruses adopt to manipulate those pathways for their benefit.

转移是指恶性细胞从原发肿瘤扩散到继发部位,给癌症治疗带来灾难性负担,也是癌症患者死亡的主要原因。转移是癌症进展的主要方面之一,可能受到病毒感染的强烈影响。事实上,病毒一直是现代癌症研究的核心,与大量癌症病例有关。病毒编码元素参与调节重要通路或特定靶点,而这些通路或靶点与癌症转移的不同阶段有牵连。考虑到新病毒的不断涌现及其对癌症进展的贡献,病毒与癌症之间的战争似乎是无止境的。在此,我们旨在回顾癌症转移所涉及的关键机制和途径,以及病毒机制的影响和病毒为自身利益操纵这些途径所采用的各种途径。
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引用次数: 0
Glutaminase 2 as a therapeutic target in glioblastoma 作为胶质母细胞瘤治疗靶点的谷氨酰胺酶 2。
IF 9.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-16 DOI: 10.1016/j.bbcan.2024.189182

Glioblastoma (GBM) is the most common malignant primary adult brain tumor. Despite standard-of-care treatment, which consists of surgical resection, temozolomide (TMZ) treatment, and radiotherapy, the prognosis for GBM patients remains poor with a five-year survival rate of 5 %. With treatment, the median survival time is 14 months, suggesting the dire need for new, more effective therapies. Glutaminolysis, the metabolic pathway by which cells can convert glutamine to ATP, is essential for the survival of GBM cells and represents a putative target for treatment. Glutamine replenishes tricarboxylic acid (TCA) cycle intermediates through glutaminolysis. The first step of glutaminolysis, the deamination of glutamine, can be carried out by either glutaminase 1 (GLS) or glutaminase 2 (GLS2). However, it is becoming increasingly clear that these enzymes have opposing functions in GBM; GLS induces deamination of glutamine, thereby acting in an oncogenic fashion, while GLS2 has non-enzymatic, tumor-suppressive functions that are repressed in GBM. In this review, we explore the important role of glutaminolysis and the opposing roles of GLS and GLS2 in GBM. Further, we provide a detailed discussion of GLS2's newly discovered non-enzymatic functions that can be targeted in GBM. We conclude by considering therapeutic approaches that have emerged from the understanding of GLS and GLS2's opposing roles in GBM.

胶质母细胞瘤(GBM)是最常见的恶性原发性成人脑肿瘤。尽管标准治疗包括手术切除、替莫唑胺(TMZ)治疗和放射治疗,但 GBM 患者的预后仍然很差,五年生存率仅为 5%。经过治疗后,中位生存期为 14 个月,这表明迫切需要更有效的新疗法。谷氨酰胺溶解是细胞将谷氨酰胺转化为 ATP 的代谢途径,对 GBM 细胞的存活至关重要,也是治疗的潜在靶点。谷氨酰胺通过谷氨酰胺分解补充三羧酸(TCA)循环中间产物。谷氨酰胺分解的第一步,即谷氨酰胺的脱氨,可由谷氨酰胺酶 1 (GLS) 或谷氨酰胺酶 2 (GLS2) 完成。然而,人们越来越清楚地认识到,这两种酶在 GBM 中具有相反的功能;GLS 诱导谷氨酰胺的脱氨,从而以致癌的方式发挥作用,而 GLS2 则具有非酶抑制肿瘤的功能,在 GBM 中受到抑制。在这篇综述中,我们探讨了谷氨酰胺溶解的重要作用以及 GLS 和 GLS2 在 GBM 中的对立作用。此外,我们还详细讨论了新发现的 GLS2 在 GBM 中的非酶功能。最后,我们考虑了通过了解 GLS 和 GLS2 在 GBM 中的对立作用而产生的治疗方法。
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引用次数: 0
Unveiling Cuproptosis: Mechanistic insights, roles, and leading advances in oncology 揭开杯状突变的神秘面纱:肿瘤学的机制认识、作用和领先进展
IF 9.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-12 DOI: 10.1016/j.bbcan.2024.189180

Copper, a vital micronutrient, performs essential functions in numerous biological settings. Its disrupted metabolism is implicated in both the initiation of tumors and therapeutic interventions for cancer, underscoring the critical necessity of preserving copper homeostasis. Cuproptosis, a regulated cell death (RCD) modulated by copper, is activated in response to elevated copper concentrations, prompting an investigation into its implication in oncogenesis. Within this review, an exploration is conducted into copper dynamics and homeostasis maintenance within cells. Furthermore, it delves into the mechanisms underlying cuproptosis and its interplay with signaling pathways implicated in cancer. The potential synergy between cuproptosis and ferroptosis and its impact on tumor immunomodulation is discussed. Additionally, promising avenues for addressing cuproptosis in cancer involve assessing the utility of copper chelators and ionophores. By addressing pressing questions surrounding cuproptosis and outlining its pivotal role in cancer pathogenesis and treatment, this review propounds targeting cuproptosis as a promising frontier in antitumor therapy, potentially revolutionizing cancer treatment strategies.

铜是一种重要的微量营养元素,在多种生物环境中发挥着重要功能。铜代谢紊乱与肿瘤的诱发和癌症的治疗干预都有关系,这突出表明了保持铜平衡的重要性。铜中毒(Cuproptosis)是一种受铜调节的细胞死亡(RCD),在铜浓度升高时会被激活,这促使人们对其在肿瘤发生中的作用进行研究。本综述探讨了铜在细胞内的动态变化和平衡维持。此外,它还深入探讨了杯突症的内在机制及其与癌症信号通路之间的相互作用。报告还讨论了铜氧化酶和铁氧化酶之间的潜在协同作用及其对肿瘤免疫调节的影响。此外,解决癌症中的铜氧化酶增多问题的可行途径还包括评估铜螯合剂和离子载体的效用。这篇综述探讨了围绕铜氧化酶的迫切问题,概述了它在癌症发病和治疗中的关键作用,认为以铜氧化酶为靶点是抗肿瘤治疗的一个前景广阔的前沿领域,有可能彻底改变癌症治疗策略。
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引用次数: 0
Matrisomics: Beyond the extracellular matrix for unveiling tumor microenvironment Matrisomics:超越细胞外基质,揭示肿瘤微环境。
IF 9.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-04 DOI: 10.1016/j.bbcan.2024.189178

The matrisome, a group of proteins constituting or interacting with the extracellular matrix (ECM), has garnered attention as a potent regulator of cancer progression. An increasing number of studies have focused on cancer matrisome utilizing diverse -omics approaches. Here, we present diverse patterns of matrisomal populations within cancer tissues, exploring recent -omics studies spanning different ‘-omics’ levels (epigenomics, genomics, transcriptomics, and proteomics), as well as newly developed sequencing techniques such as single-cell RNA sequencing and spatial transcriptomics. Some matrisome genes showed uniform patterns of upregulated or downregulated expression across various cancers, while others displayed different expression patterns according to the cancer types. This matrisomal dysregulation in cancer was further examined according to their originating cell type and spatial location in the tumor tissue. Experimental studies were also collected to demonstrate the identified roles of matrisome genes during cancer progression. Interestingly, many studies on cancer matrisome have suggested matrisome genes as effective biomarkers in cancer research. Although the specific mechanisms and clinical applications of cancer matrisome have not yet been fully elucidated, recent techniques and analyses on cancer matrisomics have emphasized their biological importance in cancer progression and their clinical implications in deciding the efficacy of cancer treatment.

基质组(matrisome)是一组构成细胞外基质(ECM)或与之相互作用的蛋白质,作为癌症进展的一个强有力的调控因子而备受关注。越来越多的研究利用不同的组学方法关注癌症基质组。在这里,我们介绍了癌症组织中基质组群体的不同模式,探讨了最近跨越不同 "组学 "水平(表观基因组学、基因组学、转录组学和蛋白质组学)的组学研究,以及新开发的测序技术,如单细胞 RNA 测序和空间转录组学。在各种癌症中,一些基质组基因表现出统一的上调或下调表达模式,而另一些基因则根据癌症类型表现出不同的表达模式。根据这些基因的起源细胞类型和在肿瘤组织中的空间位置,进一步研究了癌症中的基质组失调情况。此外,还收集了一些实验研究,以证明母体基因在癌症进展过程中的作用。有趣的是,许多关于癌症基质组的研究都认为基质组基因是癌症研究中有效的生物标志物。虽然癌症基质组的具体机制和临床应用尚未完全阐明,但最近的癌症基质组学技术和分析强调了它们在癌症进展中的生物学重要性,以及它们在决定癌症治疗效果方面的临床意义。
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引用次数: 0
Hydrogel encapsulation of mesenchymal stem cells-derived extracellular vesicles as a novel therapeutic approach in cancer therapy 水凝胶包裹间充质干细胞衍生的细胞外囊泡,作为癌症治疗的一种新疗法。
IF 9.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-01 DOI: 10.1016/j.bbcan.2024.189177

Cell therapy has emerged as one of the most promising approaches to treating disease in recent decades. The application of stem cells in anti-tumor therapy is determined by their varying capacity for proliferation, migration, and differentiation. These capacities are derived from different sources. The use of stem cell carriers in cancer treatment is justified by the following three reasons: (I) shield therapeutic agents from swift biological deterioration; (II) reduce systemic side effects; and (III) increase local therapeutic levels since stem cells have an innate ability to target tumors. The quantity of stem cells confined to the tumor microenvironment determines this system's anti-tumor activity. Nevertheless, there are limitations to the use of different types of stem cells. When immune cells are used in cell therapy, it may lead to cytokine storms and improper reactions to self-antigens. Furthermore, the use of stem cells may result in cancer. Additionally, after an intravenous injection, cells could not migrate to the injury location. Exosomes derived from different cells were thus proposed as possible therapeutic options. Exosomes are becoming more and more well-liked because of their small size, biocompatibility, and simplicity in storage and separation. A number of investigations have shown that adding various medications and microRNAs to exosomes may enhance their therapeutic effectiveness. Thus, it is essential to evaluate studies looking into the therapeutic effectiveness of encapsulated exosomes. In this review, we looked at studies on encapsulated exosomes' use in regenerative medicine and the treatment of cancer. The results imply that the therapeutic potential increases when encapsulated exosomes are used rather than intact exosomes. Therefore, in order to optimize the effectiveness of the treatment, it is advised to implement this technique in accordance with the kind of therapy.

近几十年来,细胞疗法已成为治疗疾病最有前途的方法之一。干细胞的增殖、迁移和分化能力各不相同,这决定了干细胞在抗肿瘤疗法中的应用。这些能力来自不同的来源。在癌症治疗中使用干细胞载体有以下三个理由:(1)防止治疗药物迅速发生生物退化;(2)减少全身副作用;(3)提高局部治疗水平,因为干细胞天生具有靶向肿瘤的能力。局限在肿瘤微环境中的干细胞数量决定了这一系统的抗肿瘤活性。然而,使用不同类型的干细胞也有局限性。在细胞疗法中使用免疫细胞时,可能会导致细胞因子风暴和对自身抗原的不当反应。此外,使用干细胞还可能导致癌症。此外,静脉注射后,细胞无法迁移到受伤部位。因此,从不同细胞中提取的外泌体被认为是可能的治疗方案。由于外泌体体积小、生物相容性好、易于储存和分离,因此越来越受到人们的青睐。许多研究表明,在外泌体中添加各种药物和微RNA可提高其治疗效果。因此,有必要评估有关封装外泌体治疗效果的研究。在这篇综述中,我们考察了有关封装外泌体用于再生医学和癌症治疗的研究。研究结果表明,与完整的外泌体相比,封装外泌体的治疗潜力更大。因此,为了优化治疗效果,建议根据治疗类型来实施这项技术。
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引用次数: 0
Bioactive sphingolipids as emerging targets for signal transduction in cancer development 生物活性鞘脂是癌症发展过程中信号转导的新目标。
IF 9.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-01 DOI: 10.1016/j.bbcan.2024.189176

Sphingolipids, crucial components of cellular membranes, play a vital role in maintaining cellular structure and signaling integrity. Disruptions in sphingolipid metabolism are increasingly implicated in cancer development. Key bioactive sphingolipids, such as ceramides, sphingosine-1-phosphate (S1P), ceramide-1-phosphate (C1P), and glycosphingolipids, profoundly impact tumor biology. They influence the behavior of tumor cells, stromal cells, and immune cells, affecting tumor aggressiveness, angiogenesis, immune modulation, and extracellular matrix remodeling. Furthermore, abnormal expression of sphingolipids and their metabolizing enzymes modulates the secretion of tumor-derived extracellular vesicles (TDEs), which are key players in creating an immunosuppressive tumor microenvironment, remodeling the extracellular matrix, and facilitating oncogenic signaling within in situ tumors and distant pre-metastatic niches (PMNs). Understanding the role of sphingolipids in the biogenesis of tumor-derived extracellular vesicles (TDEs) and their bioactive contents can pave the way for new biomarkers in cancer diagnosis and prognosis, ultimately enhancing comprehensive tumor treatment strategies.

鞘磷脂是细胞膜的重要组成部分,在维持细胞结构和信号完整性方面发挥着重要作用。鞘脂代谢紊乱与癌症发展的关系日益密切。关键的生物活性鞘脂,如神经酰胺、鞘氨醇-1-磷酸(S1P)、神经酰胺-1-磷酸(C1P)和糖鞘脂,会对肿瘤生物学产生深远影响。它们影响肿瘤细胞、基质细胞和免疫细胞的行为,影响肿瘤的侵袭性、血管生成、免疫调节和细胞外基质重塑。此外,鞘磷脂及其代谢酶的异常表达会调节肿瘤源性细胞外泡(TDEs)的分泌,而TDEs是创造免疫抑制性肿瘤微环境、重塑细胞外基质以及促进原位肿瘤和远处转移前壁龛(PMNs)内致癌信号传导的关键因素。了解鞘脂在肿瘤源性细胞外泡(TDEs)的生物生成过程中的作用及其生物活性成分,可以为癌症诊断和预后的新生物标记物铺平道路,最终提高肿瘤综合治疗策略的水平。
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引用次数: 0
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