TIMP1 promotes thyroid cancer cell progression through macrophage phenotypic polarization via the PI3K/AKT signaling pathway

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC

ACS Applied Electronic Materials Pub Date : 2024-08-10 DOI:10.1016/j.ygeno.2024.110914

Xu Lin , Ruhua Zhao , Yu Bin , Ronghua Huo , Gang Xue , Jingfang Wu

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Abstract

Increasing evidence suggests that tissue inhibitor of metalloproteinase 1 (TIMP1) played a pivotal role in immune regulation. Our study focused on examining the expression and function of TIMP1 in humans, particularly in its regulation of tumor-associated macrophages (TAMs) in papillary thyroid carcinoma (PTC). We observed an upregulation of TIMP1 in 16 different types of malignancies, including thyroid cancer. TIMP1 shaped the inflammatory TME in PTC. Inhibiting the expression of TIMP1 has been demonstrated to reduce the malignant biological traits of PTC cells. Furthermore, reducing TIMP1 expression impeded M2 macrophage polarization as well as facilitated M1 macrophage polarization in PTC. ELISA results demonstrated that downregulated TIMP1 expression correlated with decreased levels of IL10 and TGF-β in cell supernatants. Furthermore, the supernatant from polarized macrophages in the TIMP1-silenced group inhibited the motility of wild-type PTC cells. Therefore, TIMP1 may enhance the progression of PTC by stimulating the PI3K/AKT pathway via the secretion of IL10 and TGF-β, consequently influencing M2-type polarization in TAMs.

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TIMP1通过PI3K/AKT信号通路促进巨噬细胞表型极化，从而促进甲状腺癌细胞的进展。

越来越多的证据表明，金属蛋白酶组织抑制剂1（TIMP1）在免疫调节中发挥着关键作用。我们的研究重点是检测 TIMP1 在人类中的表达和功能，尤其是在甲状腺乳头状癌（PTC）中对肿瘤相关巨噬细胞（TAMs）的调控。我们在包括甲状腺癌在内的16种不同类型的恶性肿瘤中观察到了TIMP1的上调。TIMP1塑造了PTC中的炎性TME。事实证明，抑制 TIMP1 的表达可降低 PTC 细胞的恶性生物学特性。此外，减少 TIMP1 的表达会阻碍 M2 巨噬细胞的极化，同时也会促进 M1 巨噬细胞在 PTC 中的极化。ELISA 结果表明，TIMP1 表达的下调与细胞上清液中 IL10 和 TGF-β 水平的降低相关。此外，TIMP1 沉默组的极化巨噬细胞上清液抑制了野生型 PTC 细胞的运动。因此，TIMP1可能通过分泌IL10和TGF-β刺激PI3K/AKT通路，从而影响TAMs的M2型极化，从而促进PTC的进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Applied Electronic Materials Multiple-

CiteScore

7.20

自引率

4.30%

发文量

567