The effect of foxp3-overexpressing Treg cells on non-small cell lung cancer cells

Abstract

The aim of the present study was to investigate the novel mechanisms of forkhead box protein P3 (foxp3) in T regulatory (Treg) cells in lung cancer behavior. Treg cells were isolated from the peripheral blood of healthy volunteers and then co-cultured with 95D cells. A plasmid overexpressing foxp3 was constructed and transfected into Treg cells and an MTS assay was performed to assess cell viability. Flow cytometry was performed to evaluate cell apoptosis and reverse transcription-quantitative polymerase chain reaction was used to measure mRNA expression. A Transwell assay was used to assess cell invasion. Treg cells were successfully isolated from peripheral blood with purity of 94.26%. Foxp3 expression in Treg cells was significantly increased following co-culture with 95D cells, while matrix metalloproteinase-9 expression was upregulated in 95D cells co-cultured with Treg cells. The apoptosis, invasion and migration abilities of 95D cells were suppressed by co-culture with Treg cells, whereas the adhesive ability was enhanced. Foxp3 overexpression in Treg cells enhanced the viability and invasiveness of 95D cells, whereas cell adhesion and migration were decreased. The results of the present study demonstrate that the viability and invasiveness of 95D cells are enhanced by foxp3 overexpression in Treg cells, indicating that increased levels of foxp3 in the tumor microenvironment may promote tumor cell growth.

Molecular networks of FOXP family: dual biologic functions, interplay with other molecules and clinical implications in cancer progression

“…Thus, Treg cells suppress tumor-specific CD8 + T cell cytotoxicity through TGF-β signaling [101] and some molecules including nuclear factor of activated T cells (NFAT) [15] and Runt-related transcription factor 1 (RUNX1) [92] are found to bind to the promoter regions of FOXP3-regulated genes for activation of Treg cells. FOXP3 overexpression of Tregs may promote tumor cell growth in non-small cell lung cancer (NSCLC) microenvironment [102].…”

Bifidobacterium lactisAmeliorates the Risk of Food Allergy in Chinese Children by Affecting Relative Percentage of Treg and Th17 Cells

“…Th17 and Treg cells are the two main subsets of CD4 + T cells and participate in allergy responses [21]. FoxP3 is an intracellular transcription factor of Treg cells [22]. TGF- β plays a critical role in Treg cell development and can affect the number and function of Treg cells [23].…”

Mechanisms and Future of Non-Small Cell Lung Cancer Metastasis

“…This is exemplified by a study involving 92 patients with NSCLC, which discovered increased Treg activity in intratumoral regions, including the overexpression of FOXP3 mRNA ( 25 ). Increased level of FOXP3 is shown to enhance the viability and invasiveness of tumors in NSCLCs, thus Treg can be yet another link in immunity which lung cancer might exploit to promote its growth ( 26 ). In conclusion, diminishing effect of CD8+ T cells caused by various mechanisms corresponds to greater invasiveness of lung cancer, giving it access to more capillary beds in the lungs, which increases likelihood of blood mediated metastasis.…”