整合素β1与肿瘤的转移

整合素β1是一类介导细胞与细胞外基质及细胞与细胞间黏附的细胞黏附分子受体。整合素β1参与肿瘤转移的多个环节，在肿瘤转移中发挥着重要的作用。本文就整合素β1与肿瘤转移的关系简要综述。     

整合素β_1与肿瘤的转移

整合素β1是一类介导细胞与细胞外基质及细胞与细胞间黏附的细胞黏附分子受体。整合素β1参与肿瘤转移的多个环节，在肿瘤转移中发挥着重要的作用。本文就整合素β1与肿瘤转移的关系简要综述。     

整合素家族与肿瘤骨转移相关性研究进展

整合素家族作为黏附分子,主要介导细胞与细胞外基质间的黏附,调节许多类型肿瘤细胞的迁移、存活、增殖和血管生成等。近期许多研究证实,整合素家族还和恶性肿瘤的骨转移有着密切的关系。本文就整合素家族结构与功能、整合素家族信号通路与肿瘤转移关系、整合素与肿瘤骨转移的形成等方面进行综述。     

整合素家族与肿瘤骨转移相关性研究进展

整合素家族作为黏附分子,主要介导细胞与细胞外基质间的黏附,调节许多类型肿瘤细胞的迁移、存活、增殖和血管生成等。近期许多研究证实,整合素家族还和恶性肿瘤的骨转移有着密切的关系。本文就整合素家族结构与功能、整合素家族信号通路与肿瘤转移关系、整合素与肿瘤骨转移的形成等方面进行综述。     

整合素αvβ6在卵巢癌中的作用

整合素是一类介导细胞与细胞外基质及细胞与细胞间黏附的细胞黏附分子受体，αvβ6是整合素家族的一员，参与肿瘤的发生、发展与转移。这种作用可能是通过影响肿瘤细胞与细胞外基质黏附、细胞外基质水解、诱导肿瘤血管生成、调节肿瘤细胞凋亡等作用而实现的。深入研究αvβ6在卵巢癌中的表达与功能，有助于进一步认识卵巢癌侵袭转移的分子机制，有可能为恶性肿瘤的诊断和预后判断提供新的指标．为开发肿瘤治疗新思路提供了理论依据。     

整合素与肿瘤侵袭及转移的关系

肿瘤细胞与细胞外基质间的相互作用影响肿瘤的发生、增殖、存活和转移到其他组织的能力。许多是由分布广泛的整合素介导的。整合素是细胞黏附、细胞迁移、细胞周期和程序化死亡 (凋亡 )所必须的 ,它和其他信号途径一起调节肿瘤的发生、侵袭及转移。就整合素的结构、功能及其与肿瘤临床资料的关系予以综述     

整合素与肿瘤侵袭及转移的关系

肿瘤细胞与细胞外基质间的相互作用影响肿瘤的发生、增殖、存活和转移到其他组织的能力。许多是由分布广泛的整合素介导的。整合素是细胞黏附．细胞迁移、细胞周期和程序化死亡(凋亡)所必须的，它和其他信号途径一起调节肿瘤的发生、侵袭及转移。就整合素的结构、功能及其与肿瘤临床资料的关系予以综述。     

整合素家族与甲状腺癌

整合素作为细胞表面受体、细胞间的黏附分子,对细胞与细胞间、细胞与细胞外基质间的黏附起介导作用。近几十年来,恶性肿瘤甲状腺癌的发病率急速攀升,很大原因是由于恶性肿瘤细胞极易增殖、侵袭和转移,而这种特性与细胞表面黏附分子整合素有密切的关系。有研究发现,整合素α3β1、α6β1、αvβ3等通过与细胞间黏附分子1(ICAM-1)、血管细胞黏附分子1(VCAM-1)、血小板反应蛋白(thrombospondin, TSP)和细胞外基质胶原(collagen, CO)、层黏连蛋白(laminin, LN)、纤连蛋白(fibronectin, FN)等配体结合,激活FAK-Ras-Raf或磷脂酰肌醇3激酶(PI3K)-Akt-mTOR等信号转导通路,调控甲状腺癌细胞的生长、繁殖、侵袭和转移。通过针对整合素信号通路上多个靶点进行分子靶向干预,可能研发出甲状腺癌的针对性治疗方案。本文主要对整合素在甲状腺癌的增殖、侵袭、转移、诊断和治疗等方面所起的作用作一综述。     

肿瘤缺氧微环境与黏附分子相关性的研究进展

缺氧是一种重要的病理状态,其与肿瘤生长、发展的关系越来越多受到关注,许多研究发现缺氧与肿瘤侵袭、转移的关系密切。细胞黏附分子(cell adhesion molecule,CAM)是参与细胞与细胞之间及细胞与细胞外基质之间相互作用的分子,可大致分为5类:钙黏素、整合素、选择素、免疫球蛋白超家族及透明质酸黏素。研究证实,影响肿瘤,缺氧状态的同时也能影响相关黏附分子的表达,特别是E-cadherin、整合素分子,以及一些其他黏附分子。深入研究缺氧和这些肿瘤黏附分子之间的关系,可以为肿瘤治疗提供新的思路。     

人胃癌细胞的黏附过程和整合素β1表达的研究

目的:观察胃癌细胞黏附过程中的形态学变化,以及在此过程中整合素β1表达的部位和强度,探讨胃癌细胞黏附过程与整合素β1表达之间的关系,为抑制胃癌细胞转移的研究提供依据。方法:借助位相差显微镜观察和激光共聚焦显微镜对活体胃癌MKN1细胞黏附过程中的形态变化和整合素β1的表达部位和程度进行观察。结果:胃癌细胞首先发生形态学变化,细胞伸出伪足与培养盘和其他细胞接触形成稳定状态,在此过程中整合素β1在细胞膜的伪足部分的表达增强,并形成集落团块。结论:人胃癌MKN1细胞在黏附过程中发生形态学变化,并与整合素β1的表达增强有直接关系。     

Tumor cell adhesion to the extracellular matrix and signal transduction mechanisms implicated in tumor cell motility,invasion and metastasis

Summary The relationship between tumor cell adhesion to the extracellular matrix (ECM) and invasion and metastasis formation is one of the most intensively studied topics in cancer biology within the last 10–15 years. The aberrant molecular relationships between malignant tumor cells and their surrounding ECM have been implicated at virtually every stage of the metastatic process; ranging from steps that involve the local invasion of tumor cells away from the primary tumor to those that are involved in mediating extravasation through microvessel-associated basement membranes at the site(s) of metastasis formation. The complexity of tumor metastasis has required that a reductionist approach be taken in order to identify and relate specific molecular mechanisms involved in tumor cell adhesion to various aspects of tumor metastasis. The intensive research efforts into cell adhesion and tumor cell biology have generated many significant new concepts towards our understanding of the molecular aspects of tumor cell adhesion and metastasis. Our purpose in this article is to briefly summarize the relationship of ECM-stimulated tumor cell adhesion to the processes of tumor cell motility and invasion. This is followed by a discussion of certain aspects of signal transduction pathways that may impact on cell motility, with an emphasis on the relationship between phosphatidylinositol hydrolysis and actin polymerization, as well as certain GTP-binding protein-(G-protein) mediated events that could influence cytoskeletal organization and cell motility. Our emphasis is based on increasing evidence that implicates members of the signal transduction G-proteins in the motility and invasion of many normal and transformed cells.     

Tumor cell adhesive mechanisms and their relationship to metastasis

Despite recent advances in the diagnosis and therapy of many forms of cancer, metastasis remains the major cause of death in cancer patients. As tumors progress they become increasingly heterogeneous, giving rise to aggressive subpopulations of tumor cells that subsequently invade local tissues, the lymphatics, and the circulatory system. This invasive behavior can ultimately lead to the widespread dissemination and metastasis of the primary tumor. In hematogenous metastasis, emboli consisting of tumor cells, host cells, platelets, and fibrin are transported to distant sites where they arrest in the microvasculature prior to extravasation. It is well accepted that tumor cell adhesion plays a fundamental role in many of the stages of the metastatic process. Tumor cell interactions with extracellular matrix components of tissue, tissue boundaries (basement membranes), or cell adhesion-promoting components of plasma; influence tumor cell motility, invasiveness, and many other important aspects of the metastatic tumor cell phenotype. Tumor cell adhesion also has a rate-limiting influence at various stages within the metastatic process, such as tumor cell arrest and extravasation. In addition, the ability of the immune system to recognize and successfully eradicated tumors is also highly dependent on the adhesion of activated lymphocytes to target tumor cells. Despite the rapid accumulation of information on the molecular basis of cell adhesion, our understanding of the relationship between tumor cell adhesion and hematogenous metastasis per se is fragmented and incomplete. Nevertheless, clear progress has been made, both in understanding the molecular basis of tumor cell adhesion and its relationship to the biology of tumor metastasis. New and exciting directions have been identified that are likely to yield direct benefits in developing new therapeutic or diagnostic approaches for malignant neoplasms. Our purpose is to briefly review the molecular basis of tumor cell adhesion from the standpoint of many of the receptors involved as well as their putative ligands. The relationship between specific tumor cell adhesion events and the formation of metastatic lesions is also addressed.     

Influence of E-cadherin dysfunction upon local invasion and metastasis in non-small cell lung cancer

E-Cadherin (ECD), a transmembrane cell adhesion molecule, is associated with three kinds of cytoplasmic proteins (alpha-catenin, beta-catenin and plakoglobin), and formation of the cadherin-catenins adhesion complex is indispensable for tight cell-to-cell adhesion in adherence junctions. There is a high possibility that dysfunction of ECD reflects increased potential for local invasion and distant metastasis. We investigated the relationship between the expression of cadherin-catenin adhesion complex and the clinicopathological features in 81 cases of non-small cell lung cancer. There were statistically significant relationships between the expression of ECD and lymph node metastasis (P = 0.016) and between the expression of ECD and pathological stage (P = 0.006). Reduction of alpha-catenin expression was associated with local invasion and pathological stage. Dividing the 81 cases into two groups based on ECD function revealed a statistically significant relationship between ECD function and all clinicopathological factors investigated (local tumor invasion P = 0.033, lymph node metastasis P<0.001, pathological stage P<0.001). Evaluation of ECD function using the expression of cadherin-catenin adhesion complex is useful to evaluate tumor malignancy of non-small cell lung cancer.     

细胞黏附分子与肺癌侵袭转移的关系

细胞黏附分子(CAM)与肿瘤侵袭转移的关系密切,能够介导肿瘤细胞与细胞外基质、血管内皮细胞、实质器官组织细胞以及肿瘤细胞之间的相互作用。现就近年来细胞黏附分子在肺癌侵袭转移中的作用作一综述。     

利用基因芯片法探索人前列腺癌细胞PC-3 M在裸鼠体内淋巴道转移相关基因

背静与目的：前列腺癌是欧美国家最常见的一种男性恶性肿瘤，近年来在我国该病也有明显上升趋势。目前认为肿瘤转移是由于一部分肿瘤细胞在肿瘤生长过程中发生基因水平的变化而改变性质变成“转移克隆的细胞”，这部分细胞能突破机体防御系统最终到达远处组织器官形成转移灶。本实验旨在探索人前列腺癌细胞PC-3M在裸鼠体内淋巴道转移的相关基因，为进一步研究前列腺癌淋巴道转移机制打下一定的基础。方法：将PC-3M细胞原位接种于裸鼠体内两个月后分别从原发灶和淋巴结转移灶分离肿瘤细胞，通过体外侵袭和粘附实验，比较两者体外侵袭和粘附能力的差异，并应用基因芯片技术，检测两细胞在转移相关基因丰度水平上的差异。结果：淋巴结转移灶分离的肿瘤细胞的体外侵袭及粘附能力显著高于原发灶内分离的肿瘤细胞，大约分别为后者的2．5倍和1.5倍；而且前者在一些转移相关基因丰度水平上明显高于后者，这些基因按其编码产物的属性和功能可划分为：①编码降解细胞外基质（ECM）的蛋白水解酶包括组织蛋白酶、基质金属蛋白酶；②编码转录因子家族成员；③编码参与肿瘤细胞异质性粘附的分子；④编码细胞表面受体。结论：原发灶内的前列腺癌细胞和淋巴结转移灶内的肿瘤细胞在侵袭和粘附能力上存在显著差异，经鉴定的差异表达分子可能在前列腺癌细胞由原发灶迁移到远处组织器官的转移过程中发挥重要作用。     

P-选择素及其配体与肿瘤转移关系的研究进展

肿瘤转移为恶性肿瘤致死和临床治疗远期疗效较差的主要因素,细胞粘附为转移过程的关键步骤之一。有关研究表明Ｐ－选择素（Ｐ－ｓｅｌｅｃｔｉｎ）及其配体与肿瘤浸润、侵袭和转移灶形成有关,并有可能成为肿瘤转移的预后指标和肿瘤标志。但Ｐ－ｓｅｌｅｃｔｉｎ及其配体与肿瘤转移的关系,尤其是血小板Ｐ－ｓｅｌｅｃｔｉｎ与肿瘤癌栓形成和转移的关系仍有待进一步研究。     

缺氧-复氧增强血小板介导的肿瘤细胞-内皮细胞黏附

背景与目的:血小板能够与进入血液循环的肿瘤细胞黏附而促进其转移,但其机制是否涉及血小板作为介导物直接促进肿瘤细胞和内皮细胞黏附还不清楚,而且瘤栓在微血管局部造成的缺氧环境是否也具有促进作用尚不明确.本研究分析血小板对肿瘤细胞-内皮细胞黏附的影响及其相关黏附分子,以及缺氧-复氧在其中的作用.方法:将血小板和肿瘤细胞用荧光染料标记,通过荧光显微镜、连续光谱荧光仪以及激光共聚焦显微镜检测细胞的黏附情况;通过抗体阻断实验分析相关的细胞黏附分子,并在肠系膜血管上观察体内血小板促进肿瘤细胞在血管壁的黏附情况.结果:血小板与不同肿瘤细胞黏附能力不同,但都被缺氧-复氧所增强,并且不同肿瘤细胞与血小板的黏附被不同的抗血小板黏附分子的抗体阻断.人肝窦内皮细胞系(liver sinusoidal endothelial cell,LSEC)在缺氧-复氧后也明显增强与血小板的黏附,并且可以被抗黏附分子GP Ⅰb、GPⅡb、GPⅢa、P-selectin和CD31的抗体阻断.LSEC与血小板预温育可明显增加肿瘤细胞在其上的黏附,并且可以被抗血小板黏附分子的抗体阻断.激光共聚焦显微镜显示,血小板位于肿瘤细胞和LSEC之间,介导了两者的黏附.动物实验证实,与血小板预温育的肿瘤细胞在肠系膜血管上的黏附增多,并可以被缺血-再灌注进一步增强.结论:血小板表面存在与血管内皮细胞和肿瘤细胞同时黏附的分子,血小板通过这些黏附分子介导肿瘤细胞-内皮细胞的黏附,这种黏附作用可以被缺氧-复氧增强.     

ELAM-1靶向肿瘤转移的研究进展

目的 肿瘤的转移是恶性肿瘤致死的主要原因之一,也是影响肿瘤治疗与预后的重要因素,E选择素(endothelial leukocyte adhesion molecule-1,ELAM-1)是导致肿瘤转移的关键步骤之一,以ELAM-1为靶点成为肿瘤靶向治疗的新研究热点.本研究总结国内外对ELAM-1靶向肿瘤转移的研究进展.方法 应用ScienceDirect、PubMed及CNKI期刊全文数据库检索系统,分别以“肿瘤转移和靶向治疗、ELAM-1和肿瘤转移”等为关键词,检索2006-01-2016-12的国内外相关文献,共检索到英文文献6 092篇,中文文献7 063篇.纳入标准:(1) ELAM-1的生物学特点与生物学功能.(2)ELAM-1与常见肿瘤转移的关系.(3)ELAM-1靶向性调控与肿瘤转移情况.依据纳入排除标准,符合分析的文献27篇.结果 ELAM-1是细胞黏附分子家族的一员,其配体为唾液酸化的路易斯寡糖[sialyl-Lewis x,sLe(x)]或[sialyl-Lewis a,sLe(a)].通过ELAM-1单克隆抗体、ELAM-1分子偶联药物、ELAM-1配体sLe (x)表达抑制剂、ELAM-1/配体相互作用拮抗药物及ELAM-1表达抑制剂等可以抑制肿瘤转移、改善肿瘤预后.结论 ELAM-1与其配体的相互作用是介导肿瘤转移的关键,将ELAM-1及其调控路径作为治疗的靶点将有望成为肿瘤靶向治疗的突破口.     

Critical role of peroxisome proliferator-activated receptor gamma on anoikis and invasion of squamous cell carcinoma.

PURPOSE: Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a important role in various physiological functions. We examined whether PPARgamma is expressed in primary squamous cell carcinoma and lymph node metastasis and whether PPARgamma is a potential target for tumor therapy. EXPERIMENTAL DESIGN AND RESULTS: A high-level expression of PPARgamma was observed in tumor cells of human primary squamous cell carcinoma, lymph node metastasis, and squamous cell carcinoma cell lines. Treatment with PPARgamma-specific antagonists, but not agonists, caused apoptotic cell death on squamous cell carcinoma cell lines in a concentration-dependent manner. Small interfering RNA for PPARgamma also inhibited cell adhesion and growth of squamous cell carcinomas. The phosphorylation of focal adhesion kinase (FAK) was decreased by treatment with PPARgamma antagonists, and resulted in decreases in phosphorylation of Erk and mitogen-activated protein kinase. Furthermore, PPARgamma antagonists decreased the adhesion of squamous cell carcinomas into fibronectin-coated plates, indicating the inhibition of interaction between squamous cell carcinomas and fibronectin. Expression of integrin alpha5, a counter adhesion molecule for fibronectin, was inhibited by the treatment with PPARgamma antagonists. These results indicate that the decrease in integrin alpha5 and following inhibition of cell adhesion may cause the inhibition of FAK signaling pathways. PPARgamma antagonists also strongly inhibited invasion of squamous cell carcinoma via down-regulation of CD151 expression. CONCLUSIONS: The cell death caused by the PPARgamma antagonists was a result of direct interference with cell adhesion "anoikis" involving intracellular FAK signaling pathways. These results imply a potentially important and novel role for the inhibition of PPARgamma function via the use of specific antagonists in the treatment of squamous cell carcinoma and the prevention of tumor invasion and metastasis.