Exploring the Role of RGD-Recognizing Integrins in Cancer.
Exploring the Role of RGD-Recognizing Integrins in Cancer.
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DOI：
10.3390/cancers9090116
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发表时间：
2017-09-04
期刊：
影响因子：
5.2
通讯作者：
Kessler H
中科院分区：
文献类型：
--
作者：
Nieberler M;Reuning U;Reichart F;Notni J;Wester HJ;Schwaiger M;Weinmüller M;Räder A;Steiger K;Kessler H
整合素是细胞之间以及与其微环境之间通信的关键调节剂。整合素超家族的八个成员识别细胞外基质（ECM）蛋白中的三肽基序Arg-Gly-Asp（RGD）。这些整合素构成了一个重要的亚家族，并通过其肿瘤生物学功能在癌症进展和转移中发挥重要作用。因此，这种跨膜粘附和信号传导受体被认为是用于直接攻击癌细胞及其致命微环境的新型诊断和治疗应用的有希望的和容易获得的靶标。最近，特异性小肽和拟肽配体以及结合不同整合素亚型的抗体已被开发和合成为用于癌症治疗的新的候选药物。了解整合素亚型的不同功能和相互作用是选择性干预整合素介导的疾病的先决条件。用放射性同位素或荧光分子标记的整联蛋白亚型特异性配体允许在体内表征整联蛋白模式，随后通过亚型特异性药物进行医学干预。正在探索通过整合素配体包覆纳米颗粒、较大蛋白质或包封剂以将细胞毒性试剂直接引导至癌细胞表面。这些配体目前正在临床研究中研究其干扰肿瘤细胞粘附、迁移/侵袭、增殖、信号传导和存活的功效，从而在个性化医学中开辟新的治疗方法。
Integrins are key regulators of communication between cells and with their microenvironment. Eight members of the integrin superfamily recognize the tripeptide motif Arg-Gly-Asp (RGD) within extracelluar matrix (ECM) proteins. These integrins constitute an important subfamily and play a major role in cancer progression and metastasis via their tumor biological functions. Such transmembrane adhesion and signaling receptors are thus recognized as promising and well accessible targets for novel diagnostic and therapeutic applications for directly attacking cancer cells and their fatal microenvironment. Recently, specific small peptidic and peptidomimetic ligands as well as antibodies binding to distinct integrin subtypes have been developed and synthesized as new drug candidates for cancer treatment. Understanding the distinct functions and interplay of integrin subtypes is a prerequisite for selective intervention in integrin-mediated diseases. Integrin subtype-specific ligands labelled with radioisotopes or fluorescent molecules allows the characterization of the integrin patterns in vivo and later the medical intervention via subtype specific drugs. The coating of nanoparticles, larger proteins, or encapsulating agents by integrin ligands are being explored to guide cytotoxic reagents directly to the cancer cell surface. These ligands are currently under investigation in clinical studies for their efficacy in interference with tumor cell adhesion, migration/invasion, proliferation, signaling, and survival, opening new treatment approaches in personalized medicine.
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影响因子：
21.3
作者：
Alanko J;Mai A;Jacquemet G;Schauer K;Kaukonen R;Saari M;Goud B;Ivaska J
通讯作者：
Ivaska J
影响因子：
5.2
作者：
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通讯作者：
Sheldrake HM
影响因子：
3.2
作者：
Ahmed, N;Riley, C;Baker, MS
通讯作者：
Baker, MS
影响因子：
1.9
作者：
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通讯作者：
Whawell, Simon A.
影响因子：
7.5
作者：
Bear, James E.;Haugh, Jason M.
通讯作者：
Haugh, Jason M.