Exosomal tetraspanins mediate cancer metastasis by altering host microenvironment

// Jun Lu 3 , Jun Li 1, 2 , Shuo Liu 1, 2 , Teng Wang 1, 2 , Alessandro Ianni 4 , Eva Bober 4 , Thomas Braun 4 , Rong Xiang 1, 2 and Shijing Yue 1, 2 1 School of Medicine, Nankai University, Tianjin, China 2 The State International Science & Technology Cooperation Base of Tumor Immunology and Biological Vaccines, Nankai University, Tianjin, China 3 Department of General Surgery, Hefei Second People’s Hospital, Hefei, China 4 Department of Cardiac Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany Correspondence to: Shijing Yue, email: shijingyue@nankai.edu.cn Rong Xiang, email: rxiang@nankai.edu.cn Keywords: tumor, cancer metastasis, tetraspanin, exosomes, cancer microenvironment Received: August 04, 2016 Accepted: April 05, 2017 Published: July 10, 2017 ABSTRACT The metastases of malignant tumors develop through a cascade of events. The establishment of a pre-metastatic micro-environment is initiated by communication between tumors and host. Exosomes come into focus as the most potent intercellular communicators playing a pivotal role in this process. Cancer cells release exosomes into the extracellular environment prior to metastasis. Tetraspanin is a type of 4 times transmembrane proteins. It may be involved in cell motility, adhesion, morphogenesis, as well as cell and vesicular membrane fusion. The exosomal tetraspanin network is a molecular scaffold connecting various proteins for signaling transduction. The complex of tetraspanin-integrin determines the recruiting cancer exosomes to pre-metastatic sites. Tetraspanin is a key element for the target cell selection of exosomes uptake that may lead to the reprogramming of target cells. Reprogrammed target cells assist pre-metastatic niche formation. Previous reviews have described the biogenesis, secretion and intercellular interaction of exosomes in various tumors. However, there is a lack of reviews on the topic of exosomal tetraspanin in the context of cancer. In this review, we will describe the main characteristics of exosomal tetraspanin in cancer cells. We will also discuss how the cancer exosomal tetraspanin alters extracellular environment and regulates cancer metastasis.