胃癌腹膜转移机制的研究进展

腹膜转移是晚期胃癌常见的转移方式之一,也是导致晚期胃癌患者预后较差的主要原因。针对胃癌发生腹膜转移的机制,近年来国内外研究从外泌体、铁死亡、肿瘤微环境相关细胞群、基因和脂质代谢等多个层面开展。胃癌腹膜转移的主要分子机制逐渐成为热点议题。根据相关机制研究寻找胃癌腹膜转移的潜在治疗靶点,从而提高疗效,对改善患者生存质量及预后意义重大。文章回顾了近年来胃癌腹膜转移相关机制的国内外研究,并综述其新结果和新观点。     

外泌体对胃癌转移的作用及其在诊断中的应用研究进展

摘要胃癌是对各种治疗策略均具有一定抵抗性的恶性肿瘤之一, 其发病率及死亡率在近些年居高不下。目前胃癌的治疗方法以手术切除为主, 尽管术后辅以放化疗、免疫治疗及中医治疗等手段, 但其预后及5年生存率仍较低。目前尚缺乏高效的早期诊断胃癌的方法, 使得多数患者在晚期症状严重时才得以发现。外泌体内包含DNA、RNA、蛋白质、脂质等多种生物大分子物质, 其参与肿瘤发展的过程, 并且影响肿瘤的增殖及转移, 尤其是其中丰富的生物大分子物质可以反映肿瘤的进展程度, 这也给早期胃癌的诊断提供了新的思路, 可以将其作为非侵入性的诊断标志物。本文就外泌体在胃癌转移及早期诊断中的应用进行综述。      

外泌体在胃癌发生发展及转移中作用的研究现状及进展

外泌体是一种由各种细胞分泌的、广泛存在于人体各种体液中的直径为50~100 nm的细胞外囊泡,其囊泡内携带 DNA、microRNA(miRNA)、蛋白质及脂质等多种生物活性物质,其通过细胞间的物质交换及信号传递作用参与多种生理病理过程。目前研究显示外泌体在胃癌的早期诊断、发生发展、转移、治疗、耐药及预后等方面均发挥着重要作用。本文就外泌体在胃癌的发生发展及转移方面的研究现状及进展作一综述。     

外泌体在胃癌诊疗中的研究进展

胃癌的发病率和死亡率均较高,早诊早治极为关键,需要更加灵敏的诊断技术与精准的治疗手段,才能在胃癌早期及时发现并将其有效遏制。外泌体是细胞分泌的一种囊泡,其携带多种具有生物活性的小分子,如蛋白质、RNA、DNA等。外泌体可作为细胞间通讯的一种功能介质,传递多种生物信息并介导受体细胞的生物进程。在肿瘤中,外泌体不仅积极参与肿瘤微环境的信息传递,而且具有调节细胞免疫应答的能力。近年来外泌体在肿瘤领域的相关研究取得了一系列进展,其参与胃癌增殖、侵袭、复发和转移、耐药以及新生血管形成等方面的调控。外泌体在胃癌的早期诊断与精准治疗方面具有重要意义,值得深入探索。本文就外泌体在胃癌诊疗中的研究进展进行综述。     

外泌体在胃癌发生发展中作用的研究进展

[摘要] 外泌体通过胞内体内陷形成多泡体再与质膜融合后释放,其内含有蛋白质、脂质、核酸等生物活性物质。外泌体通过与受体细胞融合,将其内含的生物活性物质作为信号分子传递给受体细胞,从而介导细胞间信号交流。胃癌细胞分泌大量的外泌体,可影响周围细胞的功能,在调控胃癌的生物学行为中发挥重要作用。外泌体在胃癌相关研究中取得较多新进展,包括对胃癌的生长、转移、免疫逃避、耐药性等生物学行为的影响及相关机制,以及作为药物载体在胃癌靶向治疗中的临床应用。     

外泌体中circRNA-miRNA-mRNA网络在胃癌发生发展及其治疗中的作用

复杂的肿瘤微环境（TME）是导致胃癌高度异质性的主要原因之一。外泌体是多囊泡体和质膜融合后释放到体液中形成的纳米级生物囊泡，是TME中的重要组成部分。外泌体携带的生物分子通过促进细胞间的信号交流，在一定程度上参与调控癌症的发生和转移。环状RNA（circRNA）是稳定存在于外泌体中的非编码RNA，其作为miRNA 分子海绵，抑制miRNA 与mRNA 的结合，进而调节下游靶基因mRNA 的表达，并由此形成circRNA-miRNA-mRNA 网络。外泌体中circRNA-miRNA-mRNA网络通过参与调节胃癌的增殖、迁移和侵袭，诱导胃癌细胞上皮间质转化（EMT），介导胃癌血管生成，调节胃癌转移，调控胃癌的化疗耐药以及放射敏感性，在胃癌的发生发展中发挥重要作用。此外，以外泌体中circRNA 为靶点或者靶向circRNA-miRNA-mRNA网络可能为胃癌的治疗提供新的治疗选择。     

外泌体源miRNA在卵巢癌的发生和诊治中的研究进展

卵巢癌是女性常见的恶性肿瘤之一，其死亡率居妇科恶性肿瘤之首。患者就诊时通常已处于晚期，治疗效果差且易产生耐药性。故阐明卵巢癌发病的分子机制对于促进早期诊断和发现新的治疗方法至关重要。外泌体是一种携带多种物质的细胞外囊泡，包裹在外泌体中的miRNA广泛参与卵巢癌肿瘤微环境的形成、肿瘤的发生发展以及耐药性的产生，并在卵巢癌的诊治中具有较大的应用价值。本文就外泌体源miRNA在卵巢癌的发生和诊治中的研究进展进行综述。     

外泌体在肝癌发生发展中的研究进展

肝细胞癌（HCC）是最常见的恶性肿瘤之一,死亡率高,预后极差。HCC的发生涉及多种癌基因或抑癌基因的突变,但具体的分子机制尚不清楚。外泌体是细胞外囊泡的一种,可介导细胞间的物质交换和信息交流,近年来发现外泌体在肝癌的发生发展中具有关键作用,可应用于肝癌的诊断与治疗。本文就外泌体的组成与功能及其在肝癌的发生发展、诊断与治疗中的作用作一综述。     

外泌体miRNA在黑色素瘤转移和耐药中的作用

转移和耐药的发生是黑色素瘤逃脱靶向化疗药物毒性伤害的主要方式，也是导致临床靶向治疗失败和病情复发的最重要因素。外泌体是由细胞分泌的外囊泡，内含微小RNA（miRNA）、mRNA、小分子蛋白等多种生物活性物质，在肿瘤进展、诊断等方面发挥重要作用。外泌体miRNA通过协助黑色素瘤细胞穿过基底膜，诱导上皮间质转化（epithelial-mesenchymal transition，EMT），促进转移前微环境建立，参与黑色素瘤转移。同时在化疗药物治疗过程中，外泌体miRNA通过进入黑色素瘤细胞中重新激活MAPK/PI3K信号通路，进而导致耐药产生。因此，探究外泌体miRNA在黑色素瘤转移和耐药过程中的功能和机制作用对于提高和改善癌症患者的治愈率和预后状态具有重要意义。     

外泌体在肺癌中的研究进展

外泌体（exosomes）是由多种细胞分泌的具有脂质双分子层结构的纳米级膜囊小泡，其内含有蛋白质、脂质、核酸等大量生物活性物质。研究表明，外泌体在肺癌的发生发展过程中发挥着重要作用，尤其是在肺癌的早期诊断、侵袭和转移、预后评估以及治疗等方面的作用成为目前研究的热点。因此，关于外泌体的研究将在转化医学的研究模式下，为肺癌临床早期诊断、治疗及预后评估带来新的契机。本文对外泌体在肺癌中的研究进展作一综述。     

Exosomes in metastasis of colorectal cancers: Friends or foes?

Colorectal cancer (CRC), the third most common type of cancer worldwide, threaten human health and quality of life. With multidisciplinary, including surgery, chemotherapy and/or radiotherapy, patients with an early diagnosis of CRC can have a good prognosis. However, metastasis in CRC patients is the main risk factor causing cancer-related death. To elucidate the underlying molecular mechanisms of CRC metastasis is the difficult and research focus on the investigation of the CRC mechanism. On the other hand, the tumor microenvironment (TME) has been confirmed as having an essential role in the tumorigenesis and metastasis of malignancies, including CRCs. Among the different factors in the TME, exosomes as extracellular vesicles, function as bridges in the communication between cancer cells and different components of the TME to promote the progression and metastasis of CRC. MicroRNAs packaged in exosomes can be derived from different sources and transported into the TME to perform oncogenic or tumor-suppressor roles accordingly. This article focuses on CRC exosomes and illustrates their role in regulating the metastasis of CRC, especially through the packaging of miRNAs, to evoke exosomes as novel biomarkers for their impact on the metastasis of CRC progression.     

The role of pancreatic cancer-derived exosomes in cancer progress and their potential application as biomarkers

Pancreatic cancer is one of the most deadly cancers, with dismal prognosis due to its poor early detection rate and high metastatic rate. Thus, elucidation of the molecular mechanisms accounting for its metastasis and discovery of competent biomarkers is required. Exosomes are multivesicular body-derived small extracellular vesicles released by various cell types that serve as important message carriers during intercellular communication. They are also known to play critical roles during cancer-genesis, cancer-related immune reactions, and metastasis. They also possess promising potential as novel biomarkers for cancer early detection. Therefore, extensive studies on pancreatic cancer-derived exosomes are currently being performed because they hold the promising potential of elevating the overall survival rate of patients with pancreatic cancer. In the present review, we focus on the role of exosomes in pancreatic cancer-related immune reactions, metastasis, and complications, and on their potential application as pancreatic cancer biomarkers.     

The versatile role of exosomes in cancer progression: diagnostic and therapeutic implications

Background

Recent advances in cancer biology have highlighted the relevance of exosomes and nanovesicles as carriers of genetic and biological messages between cancer cells and their immediate and/or distant environments. It has been found that these molecular cues may play significant roles in cancer progression and metastasis. Cancer cells secrete exosomes containing diverse molecules that can be transferred to recipient cells and/or vice versa to induce a plethora of biological processes, including angiogenesis, metastasis formation, therapeutic resistance, epithelial-mesenchymal transition and epigenetic/stemness (re)programming. While exosomes interact with cells within the tumour microenvironment to promote tumour growth, these vesicles can also facilitate the process of distant metastasis by mediating the formation of pre-metastatic niches. Next to their tumour promoting effects, exosomes have been found to serve as potential tools for cancer diagnosis and therapy. The ease of isolating exosomes and their content from different body fluids has led to the identification of diagnostic and prognostic biomarker signatures, as well as to predictive biomarker signatures for therapeutic responses. Exosomes can also be used as cargos to deliver therapeutic anti-cancer drugs, and they can be engineered to serve as vaccines for immunotherapy. Additionally, it has been found that inhibition of exosome secretion, and thus the transfer of oncogenic molecules, holds promise for inhibiting tumour growth. Here we provide recent information on the diverse roles of exosomes in various cellular and systemic processes governing cancer progression, and discuss novel strategies to halt this progression using exosome-based targeted therapies and methods to inhibit exosome secretion and the transfer of pro-tumorigenic molecules.

Conclusions

This review highlights the important role of exosomes in cancer progression and its implications for (non-invasive) diagnostics and the development of novel therapeutic strategies, as well as its current and future applications in clinical trials.

     

外泌体miRNAs在乳腺癌肿瘤微环境中的研究进展

乳腺癌是全球女性最常发生的恶性肿瘤,患者死亡的主要原因是复发、转移和耐药性的出现。研究已经证明,外泌体介导癌细胞与肿瘤微环境之间的信息交流,外泌体携带的miRNAs通过差异表达于乳腺癌细胞,在微环境中影响癌基因表达的调控,介导乳腺癌细胞的信号通路,调节癌细胞周期进程以及重塑肿瘤相关成纤维细胞等,从而促进乳腺癌的发生、发展和转移;另外外泌体介导中和、药物外排和免疫系统抑制三种主要机制导致耐药性。未来,各种类型乳腺癌中差异表达的miRNAs有望成为临床诊断和预后的相关生物标志物,及抗肿瘤治疗的新靶点。     

The functional roles of exosomes-derived long non-coding RNA in human cancer

Cancer is one of the most pervasive causes of morbidity and mortality worldwide regardless of the fact that a majority of therapeutic strategies have been constantly invented. The survival rate of cancer patients remains unsatisfactory due to the late diagnosis, frequent metastasis and poor response to chemotherapeutics. Therefore, novel methods with high specificity and susceptibility for prompt diagnosis and precise treatment of cancer are imperative. Circulating RNA is located in bodily fluids, including urine, saliva, breast milk and naturally present in blood. Recently, long non-coding RNAs (lncRNAs), a subset of non-coding RNAs are discovered to be differentially expressed in a variety of cancers. LncRNAs have been broadly recognized as emerging mediators for cancer behavior. Presence of lncRNA in circulation can be cell-free or encapsulated in extracellular vesicles (EVs) released by cancer cells. The release of EVs, especially exosomes, with 40–120 nm diameter in size, has been implicated in the regulation of malignancies as carriers for nucleic acid cargo through intercellular transfer. Therefore, systematic understanding of the role of exosomal lncRNAs in carcinogenesis may offer ideal diagnostic and prognostic biomarker or even therapeutic targets for malignancies. Herein, the underlying functional roles of exosomal lncRNAs in regulating tumor progression, immunomodulation as well as drug resistance will be elaborated. Lastly, the importance of exosomal lncRNAs in cancer study will also be discussed.     

外泌体在癌症诊治中的作用与机制

外泌体是一种新型的癌症生物标志物，它由所有体液中各种活细胞分泌的双层纳米囊泡构成，含有丰富的蛋白质、DNA、mRNA和非编码RNA。目前外泌体被认为是细胞间通讯的另一种机制，参与细胞间交换蛋白质、脂质和遗传物质。越来越多的研究表明，外泌体在肿瘤的发生、生长、进展、转移、耐药性和免疫逃逸中发挥重要作用。在本文中，我们根据外泌体生物学的最新进展，详细阐述了外泌体影响肿瘤之间通信的具体机制，并报道了外泌体可能成为癌症诊断中有前途的生物标志物，并代表癌症治疗的新靶点。     

Exosomes play roles in sequential processes of tumor metastasis

Overwhelming evidence demonstrates that exosomes, a series of biologically functional small vesicles of endocytic origin carrying a variety of active constituents, especially tumor-derived exosomes, contribute to tumor progression and metastasis. This review focuses on the specific multifaceted roles of exosomes in affecting sequenced four crucial processes of metastasis, through which cancer cells spread from primary to secondary organs and finally form macroscopic metastatic lesions. First, exosomes modulate the primary tumor sites to assist cancer growth and dissemination. In this part, five main biological events are reviewed, including the transfer of oncogenic constituents, the recruitment and activation of fibroblasts, the induction of angiogenesis, immunosuppression and epithelial-mesenchymal transition (EMT) promotion. In Step 2, we list two recently disclosed mechanisms during the organ-specific homing process: the exosomal integrin model and exosomal epidermal growth factor receptor (EGFR)/miR-26/hepatocyte growth factor (HGF) model. Subsequently, Step 3 focuses on the interactions between exosomes and pre-metastatic niche, in which we highlight the specific functions of exosomes in angiogenesis, lymphangiogenesis, immune modulation and metabolic, epigenetic and stromal reprogramming of pre-metastatic niche. Finally, we summarize the mechanisms of exosomes in helping the metastatic circulating tumor cells escape from immunologic surveillance, survive in the blood circulation and proliferate in host organs.