TGF‐β‐mediated exosomal lnc‐MMP2‐2 regulates migration and invasion of lung cancer cells to the vasculature by promoting MMP2 expression

Abstract

Previous studies indicated that transforming growth factor (TGF)‐β‐mediated exosomal microRNAs (miRNAs) regulate the migration and invasion of lung cancer cells; however, whether and how TGF‐β‐mediated exosomal long noncoding (lnc) RNAs regulate migration and invasion of lung cancer cells remains unclear. Here, coculture experiments showed that TGF‐β pretreatment increased the migration and invasion potential of lung cancer cells and TGF‐β pretreated A549 cells increases vascular permeability. Furthermore, we found that TGF‐β‐mediated exosomes, as carriers of intercellular communication, regulated lung cancer invasion, and vascular permeability. Transcriptional analysis also revealed that lnc‐MMP2‐2 was highly enriched in TGF‐β‐mediated exosomes and might function by increasing the expression of matrix metalloproteinase (MMP)2 through its enhancer activity, with ectopic expression and silencing of lnc‐MMP2‐2 affecting lung cancer invasion and vascular permeability. Additionally, lnc‐MMP2‐2 and MMP2 expression was assessed semiquantitatively, and tissue‐specific correlations between lnc‐MMP2‐2 and MMP2 expression were evaluated. These results suggested that exosomal lnc‐MMP2‐2 might regulate the migration and invasion of lung cancer cells into the vasculature by promoting MMP2 expression, suggesting this lncRNA as a novel therapeutic target and predictive marker of tumor metastasis in lung cancer.

Exosomal Sonic Hedgehog derived from cancer‐associated fibroblasts promotes proliferation and migration of esophageal squamous cell carcinoma

“…Several signaling pathways can regulate cancer cell proliferation, migration, and invasion, however, it is unclear which one is directly involved in this phenomenon. In light of significance of TGFβ1, SHH, EGFR, and LEF‐1 in the proliferation and migration of cancer cells, we examined the differential expression of those proteins in the cell lysis solution of NFs and CAFs and paid our attention to the different expression of SHH. As previously reported, abnormal activation of Hedgehog signaling pathway was positively correlated with the clinical manifestations, lymph node metastasis, and overall survival rate of many cancers .…”

TGF-β Signaling: A Therapeutic Target to Reinstate Regenerative Plasticity in Vascular Dementia?

“…Remarkably, mobilization of exosomes is regulated by TGF-β. For example, TGF-β is involved in the transport of MMP2 containing exosomes in malignancy disorders [168]. Therefore, it can be speculated that the increased levels of TGF-β in brains with AD and VaD may play a key role in transport and accumulation of amyloid-β responsible for neurodegeneration.…”

Extracellular vesicle long non–coding RNA‐mediated crosstalk in the tumor microenvironment: Tiny molecules, huge roles

“…LncRNA H19, shuttled from CD90 + liver cancer cells to endothelial cells, promotes its tube formation and cell‐cell adhesive properties by enhancing the expression of VEGF and ICAM‐1, respectively 48 . In lung cancer, sEV lncMMP‐2‐2 upregulates vascular endothelial cell permeability upon TGF‐β stimulation 49 . It has also been reported that sEV lncRNA CCAT2 and lncRNA POU3F3 derived from glioma cells enhance endothelial cell migration, proliferation, tube formation in vitro and arteriole formation in vivo 50,51 .…”