Paolillo Mayra, Schinelli Sergio
Department of Drug Sciences, University of Pavia, Viale Taramelli 14, Pavia 27100, Italy.
Cancers (Basel). 2017 Jul 26;9(8):95. doi: 10.3390/cancers9080095.
Integrin activity and function is classically related to the bi-directional regulation of cell-extracellular matrix (ECM) contacts that regulate a number of cell pathways linked to cell adhesion, cell detachment from ECM, cell migration, and anoikis. Interestingly, emerging data continue to uncover new roles for integrins in cancer-relevant pathways, particularly concerning the regulation of immune cell activity in the tumor niche, like myeloid cell differentiation and function and, very recently, the regulation of metastatic processes by exosomes. Exosomes are deeply involved in cell-cell communication processes and several studies have shown that integrins found in tumor-associated exosomes can promote cancer progression by two novel cooperative mechanisms: horizontal transfer of integrin transcripts as vescicle cargo, and selection of target tissues to form new tumor niches during metastatic spread by integrins carried on the exosome's surface. In this review we will discuss mounting evidence that contribute to the development of a new picture for integrins in cancer, highlighting the role of integrins in the processes that leads to tumor niche formation. In particular, the role of the periostin pathway in the recruitment of tumor-associated macrophages, and the proposed contribution of exosome-derived integrins in the metastatic spread will be discussed. Finally, in light of the above considerations, an evaluation of integrins as possible therapeutic targets will be conducted.
整合素的活性和功能传统上与细胞-细胞外基质（ECM）接触的双向调节有关，这种调节涉及许多与细胞黏附、细胞与ECM脱离、细胞迁移和失巢凋亡相关的细胞途径。有趣的是，新出现的数据不断揭示整合素在癌症相关途径中的新作用，特别是在肿瘤微环境中免疫细胞活性的调节方面，如髓样细胞的分化和功能，以及最近发现的外泌体对转移过程的调节。外泌体深度参与细胞间通讯过程，多项研究表明，肿瘤相关外泌体中的整合素可通过两种新的协同机制促进癌症进展：作为囊泡货物的整合素转录本的水平转移，以及通过外泌体表面携带的整合素在转移扩散过程中选择靶组织以形成新的肿瘤微环境。在本综述中，我们将讨论越来越多的证据，这些证据有助于构建整合素在癌症中的新图景，突出整合素在导致肿瘤微环境形成的过程中的作用。特别是，将讨论骨膜蛋白途径在肿瘤相关巨噬细胞招募中的作用，以及外泌体衍生的整合素在转移扩散中的潜在作用。最后，鉴于上述考虑因素，将对整合素作为可能的治疗靶点进行评估。
