The regulation of cancer cell migration by lung cancer cell-derived exosomes through TGF-β and IL-10

Abstract

Abstract. Tumorigenesis has been considered to be as a result of abnormal cell-cell communication. It has been proposed that exosomes act as communicators between tumors and their microenvironment and have been demonstrated to be involved in tumorigenesis and subsequent metastasis. However, the mechanisms underlying the role of exosomes in these processes remains elusive. The present study sought to determine the underlying mechanisms. Using two lung cancer cell lines, it was demonstrated that exosomes derived from metastatic small cell lung cancer cells (NCI-H1688) have greater effects on cancer cell migration, compared with exosomes derived from primary non-small cell lung cancer cells (NCI-H2228). Further characterization of the contents of the exosomes demonstrated that there were increased levels of TGF-β and IL-10 in exosomes from NCI-H1688 cells compared with exosomes derived from NCI-H2228 cells, in particular under hypoxia. Blockade of TGF-β and IL-10 with antibodies confirmed that these cytokines were essential for the regulation of cancer cell migration. Taken together, the results of the present study indicated that exosomes derived from cancer cells regulated the cellular migration of tumor cells through TGF-β and IL-10, which may provide a novel approach for developing therapeutic methods against cancer.

Exosomes from high glucose-treated glomerular endothelial cells trigger the epithelial-mesenchymal transition and dysfunction of podocytes

“…For example, exosomes released from gastric cancer cells can trigger the differentiation of umbilical cord-derived mesenchymal stem cells into carcinoma-associated fibroblasts via the transfer of TGF-β 23 . Lung cancer cell-derived exosomes can regulate the tumor cells migration by transferring TGF-β 24 . In cancer, the exosomal delivery of TGF-β is capable of driving fibroblast-to-myofibroblast differentiation 25 .…”

Tumor-derived exosomes educate dendritic cells to promote tumor metastasis via HSP72/HSP105-TLR2/TLR4 pathway

“…As potent immunosuppressive cytokines, IL-10 and TGF-b1 have been demonstrated to be the mediators of TEX promotion of tumor development. [41][42][43] Building on our hypothesis, abolishment of their expression in parental cells can produce TEXs without IL-10 and/or TGF-b1, which likely convert tumor-promoting TEXs to tumor-inhibitory TEXs. In addition, in this way, TEXs with original antitumor effects might greatly increase their antitumor effect.…”

The functional role of exosome microRNAs in lung cancer

“…Exosomes can transmit mutant EGFR into tumor-associated vascular endothelial cells and activate MAPK signaling, which will promote endothelial cell proliferation [11]. Studies by Wang et al found that TGF-β and IL-10 from cancer-derived exosomes are also involved in the regulation of cell proliferation and metastasis and their high expression can promote lung cancer cell growth and metastasis [12]. Rahman et al showed that exosomes that are from high invasive potential lung cancer cells can induce the expression of vimentin in recipient cells, which will drive the recipient cells to undergo epithelial transformation, resulting in upregulation of invasion and migration ability [13].…”