Integrins and Exosomes, a Dangerous Liaison in Cancer Progression

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.