Figure 2.

TEXs support pre-metastatic niches by compromising vascular integrity, suppressing the immune system, and promoting tumor angiogenesis. (A) Exosomal miR-105 promotes vascular permeability, as indicated by the increased “appearance of intravenously injected rhodamine-dextran (red) in various organs.” Reprinted from Ref. 8. Copyright © 2014 Elsevier Inc. (B) In colorectal cancer, exosomal miR-25-3p increases vascular permeability, as indicated by the increased permeability of the human umbilical vein endothelial cell (HUVEC) monolayers to rhodamine-dextran after exposure to exosomal miR-25-3p. Reprinted from Ref 27. Copyright © 2018, The Author(s). (C) In hepatocellular carcinoma, exosomal miR-103 is linked to higher recurrence rates. Reprinted from Ref 29. Copyright © 2018 by the American Association for the Study of Liver Diseases. (D) In breast cancer, exosomal RNAs enters alveolar type II cells (AT-II cells) and causes them to secrete chemokines, hence causing neutrophil recruitment and pre-metastatic niche formation in the lungs. Reprinted from Ref. 9. Copyright © 2016 Elsevier Inc. (E) In breast cancer, TEXs increase fibronectin expression in the lungs in wild-type littermates but not in Tlr3^−/− mice. Liposomes do not seem to significantly increase fibronectin expression. Reprinted from Ref. 9. Copyright © 2016 Elsevier Inc. (F) Quantification of lung metastasis of Tlr3^−/− mice or WT littermates after exosome or liposome administration. Reprinted from Ref. 9. Copyright © 2016 Elsevier Inc. (G) In patients with ovarian cancer, high levels of exosomal soluble E-cadherin (sE-cad) are linked to worse prognoses. Reprinted from Ref. 84. Copyright © 2018, The Author(s). (H) Tube formation and angiogenesis increase when human umbilical vein endothelial cells (HUVECs) are treated with exosomes containing carbonic anhydrase-9. Reprinted from Ref. 85. Copyright © 2017 Elsevier Inc.