Integrins and Exosomes, a Dangerous Liaison in Cancer Progression.
Integrins and Exosomes, a Dangerous Liaison in Cancer Progression.
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整联蛋白和外泌体，是癌症进展的危险联络。
DOI：
10.3390/cancers9080095
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发表时间：
2017-07-26
期刊：
影响因子：
5.2
通讯作者：
Schinelli S
中科院分区：
文献类型：
--
作者：
Paolillo M;Schinelli S
整合素活性和功能典型地与细胞-细胞外基质（ECM）接触的双向调节相关，所述细胞-细胞外基质接触调节与细胞粘附、细胞从ECM脱离、细胞迁移和失巢凋亡相关的许多细胞途径。有趣的是，新出现的数据继续揭示整合素在癌症相关途径中的新作用，特别是关于肿瘤生态位中免疫细胞活性的调节，如骨髓细胞分化和功能，以及最近通过外泌体调节转移过程。外泌体深入参与细胞-细胞通讯过程，并且若干研究已经表明，在肿瘤相关外泌体中发现的整联蛋白可以通过两种新的协同机制促进癌症进展：整联蛋白转录物作为囊泡货物的水平转移，以及在转移扩散期间通过外泌体表面上携带的整联蛋白选择靶组织以形成新的肿瘤小生境。在这篇综述中，我们将讨论越来越多的证据，有助于发展一个新的图片整合素在癌症中，突出整合素的作用，导致肿瘤小生境形成的过程中。特别是，将讨论骨膜蛋白途径在肿瘤相关巨噬细胞募集中的作用，以及外泌体来源的整合素在转移性扩散中的拟议贡献。最后，鉴于上述考虑，将对整合素作为可能的治疗靶点进行评价。
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.
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