整合素与肿瘤侵袭和转移的研究进展

整合素（integrin）分布广泛[1],属于细胞黏附分子家族。研究发现整合素可以调节细胞-细胞、细胞-细胞外基质（extracellu-larmatrix,ECM〕间的黏附。整合素所介导的肿瘤细胞与ECM间的相互作用影响肿瘤的发生、增殖、侵袭和转移到其他组织的能力。现就整合素的结构、功能及其对肿瘤侵袭和转移的影响予以综述。     

以整合素为作用靶点的精氨酸-甘氨酸-天冬氨酸模体毒素研究进展

整合素为一类αβ异源二聚体膜蛋白,调节细胞外基质与胞内细胞骨架间的相互作用。精氨酸-甘氨酸-天冬氨酸（RGD）序列为整合素的结合位点,存在于多种重要的细胞外基质蛋白中。整合素与RGD序列结合可调节多种细胞生理活动,RGD模体还存在于来自蛇毒和其他物种来源的多种毒素蛋白中,这些RGD模体毒素能够特异性抑制整合素与细胞外基质的结合,从而成为整合素的强效拮抗剂。本文对整合素的结构与功能、去整合素作为整合素拮抗剂的结构特征做一综述,并对整合素和以RGD为模体结构作为潜在药物靶点的应用加以讨论。     

细胞粘附分子研究和开发的新进展

多种生理过程包括细胞的激活、迁移、增殖、分化以及其它的过程需要细胞之间、细胞与细胞外基质之间的直接接触。细胞与细胞和细胞与细胞外基质之间的相互作用是通过几种不同家族的细胞粘附分子所介导的，它们包括整合素、选择素、钙粘着蛋白和免疫球蛋白。细胞粘附分子的商业和治疗潜力在不断提高，新发现的细胞粘附分子以及某些疾病状态下整合素、选择素、免疫球蛋白新作用的发现为诊断性和治疗性药物的研究和开发提供了很好的机会     

整合素与血管内皮细胞结构及功能的研究进展

整合素(Integrin)是广泛分布在细胞表面的一类跨膜糖蛋白,属于黏附分子中细胞表面受体家族,也是细胞外基质(extracellular matrix,ECG)的主要受体,能够与其他黏附因子相互作用从而介导细胞之间的黏附[1]。整合素在血管内皮细胞的迁移、分化和维持其完整性方面起到重要的调     

透明质酸与恶性瘤的关系研究进展

人类肿瘤的发生、发展中会伴随出现基因、细胞以及机体等方面的不断变化,其中包括肿瘤细胞之间通过细胞外基质而进行的相互作用,而透明质酸作为细胞外基质的重要组成部分在这种相互作用中发挥重要作用。此文主要介绍透明质酸与恶性瘤侵袭转移之间的关系。     

整合素、黏着斑激酶与卵巢癌关系的相关研究

整合素是细胞表面的一种黏附分子,它通过介导细胞与细胞、细胞与细胞外基质间的相互作用参与细胞多种生理活动,它们与肿瘤的发生、发展以及浸润转移关系十分密切。而卵巢癌仍旧是妇科肿瘤疾病的主要死亡原因。现就整合素、黏着斑激酶与卵巢癌的研究现状进行综述。     

桩蛋白 血管内皮生长因子在胃癌组织中的表达及意义

桩蛋白是近年来发现的一种重要的细胞黏附因子,是致癌性酪氨酸激酶的一种底物,与整合素相关联,构成细胞与细胞外基质局部黏附关键部位,调节细胞的移动和播散等功能,从而提高肿瘤细胞转移和侵袭的能力。     

整合素α5β1与恶性肿瘤侵袭转移关系的研究进展

目的：综述整合素α5β1与恶性肿瘤侵袭转移的关系。方法：查阅国内外相关文献进行分析和归纳。结果：α5β1是整合素家族的一员，参与肿瘤的发生、发展与转移。而这种作用可能是通过影响肿瘤细胞与细胞外基质的黏附、细胞外基质的水解、诱导肿瘤血管的生成、调节肿瘤细胞的凋亡等作用而实现的。结论：深入研究α5β1在恶性肿瘤中的表达与功能，有助于进一步认识恶性肿瘤侵袭转移的分子机制，且有可能为恶性肿瘤的诊断和预后判断提供新的指标。     

新型蛋白Nischarin的研究进展

Nischarin是近年来在小鼠体内被发现与整合素α5亚基相互作用的一新型蛋白。研究表明,Nischarin在抑制肿瘤细胞迁移、侵袭方面发挥重要作用,还可能是天然的功能性I1-咪唑啉受体。对该蛋白的研究将有助于认识与理解抑制细胞迁移的生物学机制,开发与此蛋白相关的新型药物如肿瘤侵袭抑制剂。该文结合近年国内外关于Nischarin的研究进展做一综述。     

RGD肽介导的脑胶质瘤靶向治疗和显像的研究进展

RGD肽是含有精氨酸-甘氨酸-门冬氨酸(Arg-Gly-Asp)序列的一类短肽,能和细胞表面的整合素受体特异性结合.整合素受体,尤其是αvβ3高表达于脑胶质瘤等肿瘤细胞表面,而在成熟血管内皮细胞呈低表达.因此,在脑胶质瘤的靶向治疗和显像研究中外源性RGD肽与肿瘤细胞表面的整合素受体的竞争性结合得到广泛研究.本文综述了RGD肽介导的脑胶质瘤靶向治疗及显像的典型方法及近年来的研究进展.     

Collagen receptor integrins: rising to the challenge

Integrins are alphabeta heterodimeric receptors that connect the extracellular environment with intracellular signaling events. Integrins are important for normal development and function, but are also involved in the pathogenesis of diseases including cancer, autoimmunity and heart disease. We will review the present data on a family of integrins, the collagen receptors that include the alpha1beta1, alpha2beta1, alpha1beta1 and alpha1beta1 integrins. We will describe the knowledge gained from genetic deletion of each integrin in animal models. Mice lacking any single collagen receptor display no overt defect. However, studies using the alpha1beta1 and alpha2beta1 integrin-deficient mice indicate that these receptors play an important role in innate immunity, inflammation and autoimmunity. Finally, we will elucidate the interesting and sometimes overlapping roles for alpha1beta1 and alpha2beta1 integrins in disease and will propose potential stategies to therapeutically target these receptors to alleviate or treat disease.     

Integrins: regulators of tissue function and cancer progression

Integrins are adhesion receptors that connect cells to components of the extracellular matrix or to counter receptors on other cells. Besides mediating stable adhesion, these receptors are implicated in the deposition of extracellular matrices and they are crucial for cell migration. Integrin-mediated adhesion also modulates signal transduction cascades downstream of other receptors and thereby regulates cell survival, proliferation, and the expression of differentiation-related genes. In this review, an overview of the evidence for roles of integrins in tissue development and function is given and the contribution of changes in integrin expression to cancer is discussed.     

整合素在肿瘤转移中的作用机制研究进展

机体重要的黏附分子整合素(Integrins)在细胞与细胞外基质间及细胞与细胞间的黏附作用已为人共知。以往的研究证实整合素与肿瘤转移有着密切关系,文献分析表明,这一研究领域一直是肿瘤转移方面的研究热点,该文着重概述近5年国际上关于整合素在肿瘤转移的作用机制方面的研究进展,表明整合素介导了大量的非配体依赖的信号转导通路促进了肿瘤转移。这使得整合素在肿瘤转移中的作用机制更加明确和深入,也为整合素抑制剂的开发带来了光明的前景。     

ProteoChip-based library screening of integrin α5β1 antagonists from korean medicinal plant extracts

Integrins consist of transmembrane glycoproteins noncovalently associated to form alphabeta heterodimers. Various alpha/beta associations determine binding specieficities for cell surface molecules of the immunoglobulin superfamily as well as for extracellular matrix components. Through their cytoplasmic domains, integrins are responsible for the transmission of signals between the intracellular and the extracellular environment. We immobilized an integrin alpha5beta1 microarray on a ProteoChip to screen Korean medicinal plant extracts for binding activity. The microarray preserved the integrin alpha5beta1-fibronectin interaction, and was suppressed by the synthetic RGD peptide. We identified ten extracts with high integrin affinity using a high-throughput, competitive inhibition assay. We also demonstrate the biological function of these extracts in HUVECs.     

Integrins: novel therapeutic targets for cardiovascular diseases

Integrins are the principle mediators of molecular dialog between a cell and its extracellular matrix environment. The unique combinations of integrin subunits determine which extracellular matrix molecules are recognized by a cell. Recent studies have demonstrated that remodeling in heart and vasculature is linked to alterations in extracellular matrix and integrin expression. The roles of integrins in controlling cellular behavior have made these molecules highly attractive drug targets. New insights into mechanisms whereby the extracellular matrix takes part in the control of smooth muscle cell proliferation and cardiac growth suggest a number of putative targets for future therapies that can be applied to increase plaque stability, prevent the clinical consequences of atherosclerosis and improve outcomes after interventional procedures such as cardiac transplantation. Therapeutic candidates include antibodies, cyclic peptides, peptidomimetics and small molecules. The integrin inhibitors Integrilin and ReoPro have been approved as blood thinners in cardiovascular disease, and newer agents are undergoing testing. Although integrin function is important in the cardiovascular system, there are wide gaps in knowledge. In this review, we discuss the primary mechanisms of action and signaling of integrins in the cardiac and vascular system in normal and pathological states, as well as therapeutic strategies for targeting these molecules in the cardiovascular system.     

Integrins as attractive targets for cancer therapeutics

Integrins are transmembrane receptors that have been implicated in the biology of various human physiological and pathological processes. These molecules facilitate cell–extracellular matrix and cell–cell interactions, and they have been implicated in fibrosis, inflammation, thrombosis, and tumor metastasis. The role of integrins in tumor progression makes them promising targets for cancer treatment, and certain integrin antagonists, such as antibodies and synthetic peptides, have been effectively utilized in the clinic for cancer therapy. Here, we discuss the evidence and knowledge on the contribution of integrins to cancer biology. Furthermore, we summarize the clinical attempts targeting this family in anti-cancer therapy development.     

腺苷A1受体的作用研究进展

局部组织的缺血/缺氧常使细胞外腺苷浓度升高,腺苷通过细胞膜表面的受体将低氧的信号传入细胞内,使细胞启动低氧应对机制。腺苷受体的4种亚型在这个过程中发挥了不同的生理作用,该文是关于A1受体在保护细胞、促进免疫、调节血压及血糖等方面作用的综述。     

ROLE OF INTEGRINS IN ENTEROCYTE MIGRATION

1. Enterocyte motility depends critically on cell–matrix interactions. Although still incompletely understood, these appear critically dependent upon integrin-mediated cell adhesion.
2. In addition to providing a mechanism for cell adhesion and traction, the integrins are likely to serve as true receptors for the matrix across which cell motility occurs, initiating signals by both mechanical and chemical means that alter cell phenotype and proliferation as well as cell motility.
3. Sound rationale now exists to postulate that soluble growth factors within the extracellular milieu regulate intestinal mucosal healing not only directly but also indirectly by modulating integrin expression and organization.
Presented at the Experimental Biology Symposium on the Role of Integrins in Acute Renal Failure, New Orleans, Louisiana, USA, 1997.     

Targeting RGD recognizing integrins: drug development, biomaterial research, tumor imaging and targeting

Integrins constitute an important class of cell adhesion receptors responsible not only for cell-matrix adhesion but also for signaling bidirectionally across the membrane. Integrins are involved in many biological processes such as angiogenesis, thrombosis, inflammation, osteoporosis and cancer. Integrins thus play a key role in many severe human diseases. In this review we will describe recent research and development of RGD-containing integrin ligands for medical applications including drug design, radiolabeling, drug targeting, as well as biomaterial research. Many ligands have been developed for targeting the avb3 integrin in order to block angiogenesis or osteoporosis, but there are also other integrins like avb5 and a5b1 which become more and more interesting for similar purposes. aIIbb3 constitutes a potent target in thrombosis therapy; but the search for suitable ligands is still ongoing. We will reconstruct the drug development process for these integrin subtypes considering selected examples with focus on structure based design. Different structural requirements are pointed out concerning integrin activity and particularly the selectivity towards the distinct integrin types. Furthermore, we will show recent progress in tumor and thrombosis imaging based on radiolabeled RGD-containing ligands binding avb3 or aIIbb3, respectively. Additionally further advances in biomaterial research are presented. We describe the coating of different implant materials with various avb3 recognizing ligands for the purpose of increasing cell attachment and biocompatibility.     

Integrins as therapeutic targets

Integrins are a large family of molecules that are central regulators in multicellular biology. They orchestrate cell-cell and cell-extracellular matrix (ECM) adhesive interactions from embryonic development to mature tissue function. Diverse human pathologies involve integrin adhesion, including thrombotic diseases, inflammation, cancer, fibrosis and infectious diseases. Integrins are exciting pharmacological targets because they are exposed on the cell surface and are sensitive to pharmacological blockade, but the scale of current efforts involving integrin therapeutics continues to surprise. Several therapeutics targeting integrins are effective drugs: five have been approved for use in clinic, with combined sales of over $1.5 billion in 2010 (based on company reports from that year). We gathered information from three major drug-trial databases and found that ～260 anti-integrin drugs have entered clinical trials. Here we overview integrins as drug targets and focus on cancer.