Beyond adhesion: emerging roles for integrins in control of the tumor microenvironment.
Beyond adhesion: emerging roles for integrins in control of the tumor microenvironment.
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DOI：
10.12688/f1000research.11877.1
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
DiPersio CM
中科院分区：
文献类型：
--
作者：
Longmate W;DiPersio CM
虽然整合素最初被发现是作为细胞粘附受体，但最近的研究强化了这样的概念：整合素在癌症中的核心作用远远超出了控制细胞粘附和迁移的范围。事实上，作为跨膜细胞表面受体，在细胞和细胞外相互作用的界面上占据关键位置，并且能够进行“由内而外”和“由外而内”的信号传导，整合素具有独特的调节细胞促进、感知和反应肿瘤微环境变化的能力。此外，整合素存在于肿瘤微环境中的所有细胞类型上，它们在调节细胞间通讯中具有重要作用。数十年有希望的临床前研究表明某些整合素是癌症临床中有吸引力的治疗靶点。然而，迄今为止，针对癌症整合素的少数临床试验的结果却令人失望。重要的是，这些临床失败可能反映了肿瘤细胞和肿瘤微环境的其他细胞类型中个体和组合整合素功能的日益复杂性，以及需要探索整合素靶向药物，不仅作为单一疗法，而且作为更传统的放射疗法或化学疗法的佐剂。在这篇综述中，我们将探讨了解整合素如何调节癌症进展的最新进展，包括它们在细胞间通讯和肿瘤微环境调节中的作用。此外，我们将讨论当前癌症临床中针对整合素的努力效果有限的因素，以及克服这些挑战的潜在策略。
While integrins were originally discovered as cell adhesion receptors, recent studies have reinforced the concept that integrins have central roles in cancer that extend far beyond controlling cell adhesion and migration. Indeed, as transmembrane cell surface receptors that occupy a critical position at the interface of cellular and extracellular interactions and are capable of both “inside-out” and “outside-in” signaling, integrins are uniquely poised to regulate the cell’s ability to promote, sense, and react to changes in the tumor microenvironment. Moreover, integrins are present on all cell types in the tumor microenvironment, and they have important roles in regulating intercellular communication. Decades of promising pre-clinical studies have implicated certain integrins as attractive therapeutic targets in the cancer clinic. Nevertheless, results of the few clinical trials that target integrins in cancer have thus far been disappointing. Importantly, these clinical failures likely reflect the emerging complexity of individual and combinatorial integrin function within both tumor cells and other cell types of the tumor microenvironment, together with a need to explore integrin-targeting agents not just as monotherapies but also as adjuvants to more conventional radiotherapies or chemotherapies. In this review, we will examine recent advances toward understanding how integrins regulate cancer progression, including their roles in intercellular communication and modulation of the tumor microenvironment. Additionally, we will discuss factors that underlie the limited efficacy of current efforts to target integrins in the cancer clinic as well as potential strategies to overcome these challenges.