骨桥蛋白在肿瘤转移中的作用及机制

骨桥蛋白(OPN)是一种分泌型的钙结合磷酸化糖蛋白,参与机体的多种生理病理过程。近年来的研究表明,OPN广泛参与肿瘤细胞的黏附、移行、浸润以及转移,在恶性肿瘤的形成过程中起重要作用。本文就OPN在肿瘤侵袭、转移过程的作用及其机制进行综述。     

VEGF在恶性血液肿瘤中的作用及机制研究进展

血管内皮生长因子(vascular endothelial growth factor,VEGF)通过与其特异受体VEGFK-1、VEGFK-2、VEGFK-3等结合。在肿瘤细胞和内皮细胞始动一系列级联反应。从而发挥多样的生物学效应。对于恶性血液肿瘤细胞的生长、增生、转移、生存、稳定具有极其重要的作用。阻断其信号传导为治疗某些恶性血液肿瘤提供了一种新思路。     

血管内皮生长因子C及其受体在血液肿瘤中的研究进展

血管/淋巴管新生是生物体重要的生理过程,在恶性肿瘤进展和浸润转移过程中也发挥着重要作用。血管内皮生长因子C（VEGF-C）可通过与其受体VEGFR-2,3信号途径诱导血管/淋巴管新生。许多血液肿瘤中均有VEGF-C及受体表达,它与临床分期、耐药、疗效和预后等有一定关系。随着对其研究的深入,针对VEGF-C及其受体靶点的治疗可能成为血液肿瘤治疗的新手段。     

MALAT-1在肿瘤中的作用及其机制

肺腺癌转移相关转录1（metastasis-associated lung adenocarcinoma,MALAT-1）自首次发现以来,其在肿瘤中作用逐渐成为非编码长链RNA（long non-coding RNA,lncRNA）研究中的热点。MALAT-1主要通过调控可变剪接及直接调控编码蛋白质基因表达,参与肿瘤相关基因的表观遗传调控及相关信号转导通路,影响肿瘤生长、侵袭及转移、抗凋亡、耐药形成。本文就MALAT-1结构、生物学功能特点及其在肿瘤发生、发展中的作用和机制进行简述。     

缺氧诱导因子1在肿瘤进程中的作用机制研究

缺氧诱导因子1（hypoxia inducible factor-1,HIF-1）是介导细胞对乏氧微环境进行适应性反应的关键性转录调控因子,在肿瘤进程中可促进肿瘤血管生成、介导肿瘤代谢重编程、加速肿瘤上皮间质转化、参与肿瘤免疫逃逸、维持肿瘤干细胞特性、增加肿瘤放化疗抵抗性等,可通过多途径促进肿瘤侵袭转移,而阐明HIF-1在肿瘤进程中的作用机制可为其靶点治疗提供依据。     

趋化因子CXCL1对肿瘤的作用及其在胃癌中的研究进展

世界范围内,肿瘤是全球的主要疾病负担之一,每年造成大量的健康损害和经济损失。转移是肿瘤的基本特征,也是肿瘤致死的主要原因。大部分肿瘤患者因转移失去根治机会,部分患者术后复发转移导致治疗失败。研究肿瘤的转移机制,寻找阻断肿瘤转移的分子靶点并开发针对性药物,对提高肿瘤的治疗效果具有重要意义。胃癌是我国的主要肿瘤之一,淋巴结转移是胃癌的突出特点,因而是研究肿瘤转移的良好模型。     

miR-32 在恶性肿瘤发生发展中的作用及其机制

[摘要] 微小RNA（microRNA,miRNA）是一种内源性的长度为18~25 个核苷酸的非编码RNA,通过与蛋白质编码基因的mRNA结合来发挥重要的基因调控作用,与恶性肿瘤的发生发展密切相关。miR-32 作为miRNA家族的重要成员,在不同肿瘤中表达水平存在明显差异,因其与恶性肿瘤的相关性及本身表达的正反作用双向性,在miRNA领域受到了更多的关注。近年来研究发现,miR-32 对恶性肿瘤细胞的增殖、迁移与侵袭、自噬和凋亡均有影响。此外,miR-32 与其上游靶基因、肿瘤代谢及临床诊断和治疗也有密切的关系。本文就miR-32 在恶性肿瘤发生发展中的作用及其机制、临床诊治中应用等最新研究进展作一综述。     

Role of nitric oxide in tumor progression: Lessons from experimental tumors

Nitric oxide (NO), a potent biological mediator, plays a key role in physiological as well as pathological processes, including inflammation and cancer. The role of NO in tumor biology remains incompletely understood. While a few reports indicate that the presence of NO in tumor cells or their microenvironment is detrimental to tumor cell survival and consequently their metastatic ability, a large body of clinical and experimental data suggest a promoting role of NO in tumor progression and metastasis. We suggest that tumor cells capable of very high levels of NO production die in vivo, and those producing or exposed to lower levels of NO, or capable of resisting NO-mediated injury undergo a clonal selection because of their survival advantage; they also utilize certain NO-mediated mechanisms for promotion of growth, invasion and metastasis. The possible mechanism(s) are: (a) a stimulatory effect on tumor cell invasiveness, (b) a promotion of tumor angiogenesis and blood flow in the tumor neovasculature, and (c) a suppression of host anti-tumor defense. In this review, we discuss these mechanisms on the basis of data derived from experimental models, in particular, a mouse mammary tumor model in which the expression of eNOS by tumor cells is positively correlated with invasive and metastatic abilities. Tumor-derived NO was shown to promote tumor cell invasiveness and angiogenesis. The invasion-stimulating effects of NO were due to an upregulation of matrix metalloproteases and a downregulation of their natural inhibitors. Treatment of tumor-bearing mice with NO-blocking agents reduced the growth and vascularity of primary tumors and their spontaneous metastases. We propose that selected NO-blocking drugs may be useful in treating certain human cancers either as single agents or as a part of combination therapies.     

Nitroxoline impairs tumor progression in vitro and in vivo by regulating cathepsin B activity

Cathepsin B is a ubiquitously expressed lysosomal cysteine protease that participates in protein turnover within lysosomes. However, its protein and activity levels have been shown to be increased in cancer. Cathepsin B endopeptidase activity is involved in the degradation of extracellular matrix, a process that promotes tumor invasion, metastasis and angiogenesis. Previously, we reported an established antibiotic nitroxoline as a potent and selective inhibitor of cathepsin B. In the present study, we elucidated its anti-tumor properties in in vitro and in vivo tumor models.Tumor and endothelial cell lines with high levels of active cathepsin B were selected for functional analysis of nitroxoline in vitro. Nitroxoline significantly reduced extracellular DQ-collagen IV degradation by all evaluated cancer cell lines using spectrofluorimetry. Nitroxoline also markedly decreased tumor cell invasion monitored in real time and reduced the invasive growth of multicellular tumor spheroids, used as a 3D in vitro model of tumor invasion. Additionally, endothelial tube formation was significantly reduced by nitroxoline in an in vitro angiogenesis assay. Finally, nitroxoline significantly abrogated tumor growth, angiogenesis and metastasis in vivo in LPB fibrosarcoma and MMTV-PyMT breast cancer mouse models. Overall, our results designate nitroxoline as a promising drug candidate for anti-cancer treatment.     

组织因子与肿瘤

近年来认为肿瘤的血管生成、侵袭和转移与凝血高度相关,其中一个关键蛋白就是组织因子(TF)。TF可作为细胞内信号传导介质,改变基因表达形式和细胞行为,明确参与肿瘤相关性血管生成,其表达量与多种肿瘤转移相关。抗血管生成和TF靶向治疗阻止肿瘤生长和转移,有望成为一种新的抗肿瘤治疗方法。     

组织因子与肿瘤

近年来认为肿瘤的血管生成、侵袭和转移与凝血高度相关,其中一个关键蛋白就是组织因子（TF）。TF可作为细胞内信号传导介质,改变基因表达形式和细胞行为,明确参与肿瘤相关性血管生成,其表达量与多种肿瘤转移相关。抗血管生成和TF靶向治疗阻止肿瘤生长和转移,有望成为一种新的抗肿瘤治疗方法。     

免疫微环境促进肿瘤发生发展的机制研究进展

机体免疫有宿主保护和肿瘤促进双重作用免疫微环境对肿瘤的促进作用知之甚少。研究发现本文讨论免疫微环境可直接或间接地影响肿瘤的发生发展,其机制。其机制包括促进肿瘤血管生成、改变肿瘤的生物学特性、筛选适应微环境的肿瘤细胞存活或建立适宜的肿瘤微环境促进肿瘤进展,甚至可以调节肿瘤干细胞活性。基于免疫微环境在肿瘤发生发展中的重要作用,免疫治疗成为一种重要的抗肿瘤治疗手段,而探索免疫治疗和细胞毒药物或分子靶向药物联合的多模式治疗可能是未来肿瘤免疫治疗的方向。     

The role of matrix metalloproteinases in tumor angiogenesis and tumor metastasis

Although a considerable amount of effort has been placed on discovering the etiologies of cancer, the majority of the basic cancer research existing today has focused on understanding the molecular mechanism of tumor formation and metastasis. Metastatic spread of tumors continues to be a major obstacle to successful treatment of malignant tumors. Approximately 30% of those patients diagnosed with a solid tumor have a clinically detectable metastasis and for the remaining 70%, metastases are continually being formed throughout the life of the tumor. Even after the tumor is excised, the threat of death is attributable to the metastasis that may occur through the remaining tumor cells. In addition, treating the metastasis often proves futile since metastasis often vary in size, composition, and anatomical location. New treatments blocking the formation of metastasis will provide greater chances of survival for cancer patients. One family of enzymes that has been shown over the years to play a role in tumor progression is the matrix metalloproteinase (MMP) family. The main function of MMPs, also known as matrixins, is degradation of the extracellular matrix physiologic function involving MMPs include wound healing, bone resorption and mammary involution. MMPs, however, also contribute to pathological conditions including rheumatoid arthritis, coronary artery disease, and cancer. Tumor cells are believed to utilize the matrix degrading capability of these enzymes to spread to distant sites. In addition, MMPs also are thought to promote the growth of these tumor cells once they have metastasized. This review will discuss the role of MMPs and their inhibitors in tumor invasion, angiogenesis and metastasis with special emphasis on the gelatinases, MMP-2 and MMP-9.     

黏着斑激酶活化与肿瘤进程研究进展

细胞质非受体型酪氨酸激酶黏着斑激酶（focaladhesionkinase，FAK），作为信号转导的关键分子，传递由胞外基质到细胞质的信号，在许多高度恶化肿瘤中表达升高，并促进细胞形态学变化、形成伪足小体和侵袭伪足，进而导致入侵表型的出现。因此，研究FAK的结构、功能以及在细胞运动、细胞存活、肿瘤发生过程中的作用意义重大。本文就FAK的活化以及在肿瘤发生过程中的作用作一综述。     

Src family kinases in tumor progression and metastasis

The Src family of non-receptor protein tyrosine kinases plays critical roles in a variety of cellular signal transduction pathways, regulating such diverse processes as cell division, motility, adhesion, angiogenesis, and survival. Constitutively activated variants of Src family kinases, including the viral oncoproteins v-Src and v-Yes, are capable of inducing malignant transformation of a variety of cell types. Src family kinases, most notably although not exclusively c-Src, are frequently overexpressed and/or aberrantly activated in a variety of epithelial and non-epithelial cancers. Activation is very common in colorectal and breast cancers, and somewhat less frequent in melanomas, ovarian cancer, gastric cancer, head and neck cancers, pancreatic cancer, lung cancer, brain cancers, and blood cancers. Further, the extent of increased Src family activity often correlates with malignant potential and patient survival. Activation of Src family kinases in human cancers may occur through a variety of mechanisms and is frequently a critical event in tumor progression. Exactly how Src family kinases contribute to individual tumors remains to be defined completely, however they appear to be important for multiple aspects of tumor progression, including proliferation, disruption of cell/cell contacts, migration, invasiveness, resistance to apoptosis, and angiogenesis. This review details the evidence for Src family activation in human tumors, and emphasizes possible consequences to tumor progression. Given the ability of Src and its family members to participate in so many aspects of tumor progression and metastasis, Src family kinases are attractive targets for future anti-cancer therapeutics.     

循环肿瘤细胞自我种植在恶性肿瘤进展中的作用及研究进展

肿瘤循环肿瘤细胞(circulating tumor cells,CTCs)自我种植现象的发现提示了CTCs的双向运行,即CTCs除远处播散定植形成转移外,能够随循环再次种植原发灶并促进原发灶的生长,为恶性肿瘤的生长、转移和复发等恶性进展提供了新的解释.新近研究揭示了CTCs自我种植过程中发挥作用的关键因子及具体机制,...     

轴突导向蛋白4D 在肿瘤进展中的作用*

轴突导向蛋白4D（SEMAPHORIN 4D,SEMA 4D）又称CD100,是轴突导向蛋白Ⅳ亚族（SEMAs Ⅳ）的重要成员之一,其最初作为影响神经发育的轴突导向分子被发现。近来越来越多的研究表明,SEMA 4D 在免疫调节、血管发生及肿瘤生长转移等方面也有重要的生物学功能,尤其作为新的促血管生成分子,SEMA 4D 的相关研究引起广泛关注。本文旨在对SEMA 4D 的结构、受体特点、促血管生成及肿瘤侵袭转移等方面的最新研究进展进行综述。