Table 1.

Summary of functional molecules in TEXs.

Functional molecule	Summary of mechanism
Makes vasculature leaky
miR-105	Lowers zonula occludens-1 (ZO-1) levels in endothelial cells
miR-25-3p	Silence Krüppel-like factor 2 (KLF2) and Krüppel-like factor 4 (KLF 4) in colorectal cancer
miR-103	In liver cancer, inhibits the expression of the VE-cadherin, P120, and ZO-1
Immunosuppression
PD-L1	Binds to PD-1 on cytotoxic T-cells, blocks signaling downstream of the T-cell receptor (TCR), and hence inactivates them.
Noncoding Y RNA hY4	Helps reprogram monocytes in an immunosuppressive manner by activating endosomal TLR7/TLR8 signaling; increases TNF-alpha and PD-L1 expression
gp130	An IL-6 receptor; in breast cancer, stimulates STAT3 signaling in bone-marrow derived macrophages and triggers IL-6 secretion
MET	A hepatocyte growth factor receptor; educates bone-marrow derived cells to make them pro-vasculogenic and pro-migratory
miR-1246	Increases macrophages' TGF-β activity and makes them more motile and invasive, undergo epithelial-to-mesenchymal transition, degrade the extracellular matrix, and recruit immunosuppressive Tregs
miR-92a	By suppressing SMAD7 protein, increases TGF-β activity in hepatic stellate cells and deposition of extracellular matrix proteins in the pre-metastatic niche, promoting the recruitment of immunosuppressive BMDCs
Promotes metastatic niches
Binding of disseminated tumor cells to metastatic niches
ITGβ4	On exosome's surface; binds to laminin in the laminin-rich lung microenvironment
ITGα6β4	On exosome's surface; binds to epithelial cells and fibroblasts that belong to the lung
ITGαv	May selectively adhere to fibronectin in the fibronectin-rich microenvironment in the liver
Angiogenesis in metastatic niche
Soluble E-cadherin	Binds to VE-cadherin on endothelial cells and hence activates NF-κB and β-catenin signaling
Carbonic anhydrase 9 (CA9)	Induces tube formation and migration and increases MMP2 production