Longmate Whitney, DiPersio C Michael
Department of Regenerative and Cancer Cell Biology, Albany Medical College, Albany, New York, USA.
Department of Surgery, Albany Medical College, Albany , New York, USA.
F1000Res. 2017 Aug 31;6:1612. doi: 10.12688/f1000research.11877.1. eCollection 2017.
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.
虽然整合素最初被发现是细胞粘附受体，但最近的研究强化了这样一种观念，即整合素在癌症中发挥着核心作用，其作用远远超出控制细胞粘附和迁移。事实上，作为跨膜细胞表面受体，整合素在细胞与细胞外相互作用的界面占据关键位置，并且能够进行“由内向外”和“由外向内”信号传导，因此整合素具有独特的优势来调节细胞促进、感知肿瘤微环境变化并做出反应的能力。此外，整合素存在于肿瘤微环境中的所有细胞类型上，并且在调节细胞间通讯中发挥重要作用。数十年来，有前景的临床前研究表明某些整合素是癌症临床治疗中颇具吸引力的治疗靶点。然而，迄今为止，针对癌症中整合素的少数临床试验结果令人失望。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中其他细胞类型内个体和组合整合素功能的日益复杂性，同时也需要探索整合素靶向药物，不仅作为单一疗法，而且作为更传统放疗或化疗的辅助药物。在这篇综述中，我们将研究在理解整合素如何调节癌症进展方面的最新进展，包括它们在细胞间通讯和肿瘤微环境调节中的作用。此外，我们将讨论当前在癌症临床中靶向整合素的努力疗效有限的潜在因素，以及克服这些挑战的潜在策略。
