Depression of ETS variant 1 (ETV1) levels inhibited the progression of gastrointestinal stromal tumor (GIST) cells, according to a study published in the Journal of Clinical Biochemistry and Nutrition.
The study validated a previous observation that increased ETV1 expression was linked to GIST pathogenesis. Knockdown of ETV1 expression halted the progression of GIST cells induced through M2 polarization of tumor-associated macrophages (TAMs). ETV1 silencing reduced cell proliferation and invasion and promoted apoptosis.
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“All in all, the present study validated the upregulation of ETV1 in GIST development and depressing ETV1 dramatically inhibited the malignant progression of GIST cells induced by M2-[polarized] TAM,” the authors wrote.
Coculturing undifferentiated TAMs with GIST cells with silenced ETV1 dramatically reduced the expression of CD206 and Agr-1, proteins related to the M2 polarization of TAM. Reductions in M2-type TAM cytokines including transforming growth factor beta (TGF-β) and interleukin 6 (IL-6) were also observed in this cocultured environment.
“We also demonstrated the association between ETV1 and M2-polarization of infiltrated TAM in GIST microenvironment, emphasizing the crucial role of ETV1 in the interaction between TAM and GIST cells, as well as GIST pathogenesis. This evidence may provide a new target of GIST regulation,” the authors suggested.
The expression of phosphodiesterase 3A (PDE3A), which is generally associated with cell proliferation, inflammation, metabolism, and differentiation, was also found to be upregulated in GIST tissues and cells compared to nontumor tissues and cells. PDE3A expression was found to be positively correlated with ETV1 and CD206 levels, indicating that it may be involved in the ETV1-regulated M2 polarization of TAMs.
ETV1 expression levels were evaluated in paired tissue samples taken from 32 patients with GIST. ETV1 levels were upregulated in GIST tissues compared to adjacent nontumor tissues. Elevated expression of ETV1 was also observed in 2 GIST cell lines including GIST-T1 and GIST-882.
Guo X, Li Y, Wan B, et al. ETV1 inhibition depressed M2 polarization of tumor-associated macrophage and cell process in gastrointestinal stromal tumor via down-regulating PDE3A. J Clin Biochem Nutr. Published online March 1, 2023. doi:10.3164/jcbn.22-47