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Table 3 Exosomes related with lung cancer metastasis by the regulation of immune and angiogenesis

From: Tumor-associated exosomes promote lung cancer metastasis through multiple mechanisms

Cancer type Exosomes source Related genes or pathway Tissues and/or cells Experimental data Function Refs
Immune regulation
 Lung cancer (NSCLC) Cell culture fluid PD-L1 Lung cancer cells Reduce T cell activity resulting in immune escape, and promote tumor growth Immune inhibition; immune escape [47]
 Lung cancer Lung cancer cells (LLC Lewis) PD-L1 LLC Lewis lung carcinomacells Tumor exosome treatment can inhibit the maturation and migration of DCs and promote DCs immunosuppression Immune inhibition [48]
 Lung cancer Tumors secreting miR-21; miR-29a; TLR7; TLR8 Lung cancer cells (A549) miR-21 and miR-29a bind to TLR7 and TLR8, triggering a TLR-mediated prometastatic inflammatory response that leads to tumor growth and metastasis Immune inhibition [49]
 Lung cancer TD-MVs TGF-β1; miR-23a Lung cancer cells TD-MVS transferred TGF-β1 into NK cells and inhibited NK cell function under hypoxia Immune inhibition [50]
 Lung cancer Patients serum EGFR Lung cancer patients Induction of immune tolerance in dendritic cells by inhibiting tumor antigen-specific CD8 + T cells Immune inhibition [51]
 Lung cancer MDA-MB-231 cell culture fluid miR-126; PTEN/PI3K/ Akt signaling pathway Lung cancer cells (A549) MDA-MB-231 cell-derived exosomes can recognize A549 cells in the blood and effectively escape from in vitro immune monitoring systems; miR-126–231-Exo strongly inhibits the proliferation and migration of A549 cells by blocking the PTEN/PI3K/ Akt signaling pathway Immune escape [52]
Angiogenesis regulation
 Lung cancer Cell culture fluid miR-23a; PHD1; PHD2; ZO-1 Lung cancer cells miR-23a up-regulated in exosomes of lung cancer under hypoxic conditions. miR-23a inhibits PHD1 and 2, leading to HIF-1 accumulation to enhance angiogenesis and, in addition, inhibits ZO-1, increases vascular permeability and cancer transepithelial migration Enhance angiogenesis [53]
 Lung cancer Cell culture fluid (malignant transformation of HBE cells) exosomal miR-21; STAT3; VEGF HBE cells miR-21 in exosomes activates STAT3, increases VEGF levels in recipient cells, and promotes angiogenesis and malignant transformation of HBE cells Enhance angiogenesis [54]
 Lung cancer Serum from patients with NSCLC exosomal miR-126 HBE cells miR-126 in exosomes induces angiogenesis and malignant transformation of HBE cells. Enhance angiogenesis [55]
 Lung cancer Lung cancer cells secreting (Hypoxic conditions) HIF-1α; COX-2; miR-135b; miR-210 Lung cancer cells (A549) Hypoxia-induced exosomes can promote the proliferation, migration and angiogenesis of A549 cells.
Aspirin attenudes this stimulative effect by inhibiting the proliferation of hypoxic A549 cells, reducing exosome secretion and changing exosome composition.
Enhance angiogenesis [29]
 Lung cancer (SCLC) NCI-H69 SCLC cells secreting sFlt-1 HUVECs Exosomes of SCLC cell lines contain very low level of sFlt-1, which significantly increases the migration of HUVECs and weakens the inhibitory effect of NCI-H69-Exo on angiogenesis. Enhance angiogenesis [56]
 Lung cancer TECs (derived from ADC and SCC) CDH2; MAPK/ERK and MAPK/JNK signaling pathways Lung cancer patients CDH2 significantly promoted angiogenesis in vivo and in vitro. Enhance angiogenesis [57]
  1. Abbreviations: ADC Adenocarcinoma, CDH2 Cadherin-2, DCs Dendritic cells, HBEs Human bronchial epithelial cells, HUVEC Human umbilical vein endothelial cells, PHD Prolyl hydroxylase, TD-MVs Tumor-derived microvesicles, TECs Tumor-derived endothelial cells, TLR Toll-like receptor, NSCLC Non-small cell lung cancer, SCC Squamous cell carcinoma, SCLC Small cell lung cancer, sFlt-1 Soluble fms-like tyrosine kinase-1, VEGF Vascular endothelial growth factor