Cancer-Associated Fibroblasts Promote the Proliferation and Migration of Endometrial Carcinoma Cells by Enhancing Ferroptosis Resistance

Abstract

Objectives: To explore the effects of cancer-associated fibroblasts (CAFs) on the proliferation, migration, invasion and ferroptosis of endometrial cells. Methods: The fibroblast activation protein (FAP), alpha-smooth muscle actin (α-SMA) and glutathione peroxidase 4 (GPX4) levels in endometrial tissues of patients with endometrial carcinoma (EC), endometrial hyperplasia (EH) and proliferative endometrium (PE) were detected by immunohistochemistry. CAFs and Ishikawa cells were co-cultured using a Transwell®. The cell proliferation rate, invasion ability and migration ability were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay and Transwell® assay were used for determining. Biochemical assays were employed to measure Fe²⁺ levels in cells. Western blotting was performed to observe the GPX4 protein expression level in the cells. Results: Compared with patients suffering from EH, patients with EC exhibited higher α-SMA, FAP and GPX4 levels in endometrial tissue. The α-SMA, FAP and GPX4 levels in both EC and EH patients were higher than that in PE patients. Compared with the normal endometrial fibroblasts (NEFs) group, the proliferation rate, migration ability, invasion ability and GPX4 protein expression levels of Ishikawa cells in the CAFs group were obviously raised, while the Fe²⁺ level was notably lowered. Conclusions: EC-derived CAFs promote EC cells to proliferate, migrate and invade, as well as inhibit ferroptosis.