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. Author manuscript; available in PMC: 2019 Jan 1.
Published in final edited form as: Biochim Biophys Acta. 2017 Nov 24;1869(1):64–77. doi: 10.1016/j.bbcan.2017.11.005

Figure 1. Premetastatic niche formation.

Figure 1

Extracellular act as emmisaries for primary tumors that metastasize to distant organs. PDAC cells secrete EVs enriched in Macrophage migration inhibitory factor (MIF) that trigger TGF-β secretion by Kupffer cells in the liver. TGF-β enhances fibronectin (FIN) expression by hepatocytes, which helps recruit bone-marrow derived cells and initiates PMN formation. CD105+ Renal carcinoma cells release EVs containing pro-angiogenic miRNAs and mRNAs that upregulate angiogenesis in healthy lung epithelial cells, thereby initiating blood vessel formation for secondary tumors. Melanoma cells secrete EVs that carry small nuclear RNAs (snRNAs) known to upregulate toll-like receptor (TLR3) expression on the surface of lung endothelial cells, leading to neutrophil recruitment. PDAC cells that are CD44v-positive secrete EVs that are enriched in hepatocyte growth factor (HGF). These EVs act as triggers for activation of leukocytes, fibroblasts and endothelial cells leading to PMN formation within the lungs. However, their action is dependent on CD44v-positive extracellular matrix.