Emerging Roles of Tumor Exosomes in Cancer Progression

Abstract

Metastasis is the most devastating outcome of cancer, accounting for the major cancer death. To conquer the deadly spread of cancer cells, many metastasis mediators, including exosomes, have been identified. As an extracellular component, exosomes contribute to cancer cells communication with distant organs to create a metastatic niche suitable for later colonization of cancers. Nevertheless, the determinants and their regulatory mechanisms of tumor-derived exosomes in mediating organotropism, pre-metastatic niche formation and cancer metastasis are beginning to emerge. As proposed by Stephen Paget in 1889, the “ seed and soil” hypothesis implicates an organotropic metastasis in cancers. Recently, we have determined that tumor exosomal integrins are key determinants for guiding organotropic targeting and the sequential Src phosphorylation and pro- inflammatory S100 gene expression happens in the recipient cell. Therefore, a pre-metastatic niche is created for subsequent cancer metastasis. Blocking of exosomal integrins, such as α6β4 and α6β 1 were associated with lung metastasis, impaired lung metastasis. Furthermore, the expression of β 4 integrin in both tumor cells and tumor-derived exosomes is crucial for malignant development and organotropic metastasis of breast cancer, respectively. The congruity of β4 integrin expression in cells and tumor exosomes is thought to be selective and regulated despite little is known. Here, we also attempt to elucidate the regulatory mechanism of exosomal β4 integrin in terms of biogenesis, activity, uptake and signaling. Together, these data indicate tumor exosomes used for prediction and therapeutic targets of cancer metastasis. [1] Ayuko Hoshino*, Bruno Costa-Silva*, Tang-Long Shen*, et al. (2015) Tumor exosome integrins determine organotropic metastasis. Nature 527(7578):329-35 (*co-first authors) [2] Yu-Ling Tai, Pei-Yu Chu, I-Rui Lai, Hui-Yuan Tseng, Jun-Yang Liou, Jun-Lin Guan, Tang-Long Shen* (2015) An EGFR/Src-dependent b4 Integrin/FAK complex contributes to the malignancy of breast cancer. Scientific Reports 5 , 16408