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棕色脂肪细胞通过诱导 PPAR-γ/UCP2 的表达促进神经母细胞瘤细胞的上皮间质转化。

Brown adipocytes promote epithelial mesenchymal transition of neuroblastoma cells by inducing PPAR-γ/UCP2 expression.

机构信息

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, Northern China, China.

Nuclear Medicine Department, Beijing Friendship Hospital, Capital Medical University, Beijing, Northern China, China.

出版信息

Adipocyte. 2022 Dec;11(1):335-345. doi: 10.1080/21623945.2022.2073804.

Abstract

Neuroblastoma (NB) is an embryonic malignant tumour of the sympathetic nervous system, and current research shows that activation of brown adipose tissue accelerates cachexia in cancer patients. However, the interaction between brown adipose tissues and NB remains unclear. The study aimed to investigate the effect of brown adipocytes in the co-culture system on the proliferation and migration of NB cells. Brown adipocytes promoted the proliferation and migration of Neuro-2a, BE(2)-M17, and SH-SY5Y cells under the co-culture system, with an increase of the mRNA and protein levels of UCP2 and PPAR-γ in NB cells. The UCP2 inhibitor genipin or PPAR-γ inhibitor T0090709 inhibited the migration of NB cells induced by brown adipocytes. Genipin or siUCP2 upregulated the expression of E-cadherin, and downregulated the expression of N-cadherin and vimentin in NB cells. We suggest that under co-cultivation conditions, NB cells can activate brown adipocytes, which triggers changes in various genes and promotes the proliferation and migration of NB cells. The PPAR-γ/UCP2 pathway is involved in the migration of NB cells caused by brown adipocytes.

摘要

神经母细胞瘤(NB)是一种起源于交感神经系统的胚胎恶性肿瘤,目前的研究表明,棕色脂肪组织的激活会加速癌症患者的恶病质。然而,棕色脂肪组织与 NB 之间的相互作用尚不清楚。本研究旨在探讨共培养体系中棕色脂肪细胞对 NB 细胞增殖和迁移的影响。在共培养体系中,棕色脂肪细胞促进了 Neuro-2a、BE(2)-M17 和 SH-SY5Y 细胞的增殖和迁移,NB 细胞中 UCP2 和 PPAR-γ 的 mRNA 和蛋白水平增加。UCP2 抑制剂京尼平或 PPAR-γ 抑制剂 T0090709 抑制了棕色脂肪细胞诱导的 NB 细胞迁移。京尼平或 siUCP2 上调了 NB 细胞中 E-钙黏蛋白的表达,下调了 N-钙黏蛋白和波形蛋白的表达。我们认为,在共培养条件下,NB 细胞可以激活棕色脂肪细胞,这会引发各种基因的变化,并促进 NB 细胞的增殖和迁移。PPAR-γ/UCP2 通路参与了棕色脂肪细胞诱导的 NB 细胞迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c436/9122313/5ef931be0da2/KADI_A_2073804_F0001_OC.jpg

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