Cancer-Derived Transforming Growth Factor-beta Modulates Tumor-Associated Macrophages in Ampullary Cancer

doi:10.2147/OTT.S246714

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Please use this identifier to cite or link to this item: https://ir.cnu.edu.tw/handle/310902800/34094

Title:	Cancer-Derived Transforming Growth Factor-beta Modulates Tumor-Associated Macrophages in Ampullary Cancer
Authors:	Cheng, Li-Chin Chao, Ying-Jui Wang, Chih-Yang Phan, Nam Nhut Chen, Yi-Ling Wang, Tzu-Wen Hsu, Hui-Ping Lin, Yih-Jyh Shan, Yan-Shen Lai, Ming-Derg
Contributors:	Chi Mei Med Ctr, Dept Surg, Div Colorectal Surg Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Surg Natl Cheng Kung Univ, Coll Med, Inst Clin Med Natl Cheng Kung Univ, Coll Med, Dept Biochem & Mol Biol Natl Cheng Kung Univ, Coll Med, Inst Basic Med Sci Taipei Med Univ, Coll Med Sci & Technol, Program Canc Mol Biol & Drug Discovery Taipei Med Univ, Coll Med Sci & Technol, Grad Inst Canc Biol & Drug Discovery Nguyen Tat Thanh Univ, NTT Inst Hitechnol Chia Nan Univ Pharm & Sci, Senior Citizen Serv Management Vanderbilt Univ, Dept Biostat, Med Ctr, Nashville
Keywords:	ampullary cancer tumor-associated macrophages transforming growth factor-beta bioinformatics
Date:	2020
Issue Date:	2022-11-18 11:23:41 (UTC+8)
Publisher:	Dove Medical Press Ltd
Abstract:	Purpose: Tumor-associated macrophages (TAMs) originate from monocytes and differentiate into mature macrophages. The interaction between cancer cells and TAMs promotes tumor growth and suppresses immunosurveillance. However, this phenomenon has seldom been observed in ampullary cancer. Patients and Methods: TAMs in ampullary cancer were investigated using immunohistochemical (IHC) staining of cancer tissues. Bioinformatic analysis of data from the Gene Expression Omnibus (GEO) database revealed transforming growth factor-beta (TGF-beta signaling in ampullary cancer. The complementary DNA microarray of cancer was compared with adjacent normal duodenum and enzyme-linked immunosorbent assay of serum was used to verify TGF-beta signaling in patients. The THP-1 cell line was activated in vitro to imitate M2 TAMs. ClueGo and CluePedia software were operated to simulate TGF-beta-related networks in ampullary cancer. Results: The IHC study revealed that the majority of TAMs inside ampullary cancer were cluster of differentiation (CD)163(+) cells and that the expression of mature CD68(+) macrophages was correlated with advanced cancer stage. Bioinformatics analysis revealed that TGF-beta and its downstream signaling were significantly upregulated. To verify our bioinformatics-derived predictions, we performed several experiments and demonstrated that increased TGF-beta expression was detected in the cDNA microarray. Higher serum levels of TGF-beta were correlated with fewer CD68(+) and more inducible nitric oxide synthase macrophages in ampullary cancer. Treatment with TGF-beta induced modulation of THP-1-derived macrophages. Conclusion: The present study demonstrates that TGF-beta modulates macrophage activity in ampullary cancer. Targeting TGF-beta could be an approach to activating immunosurveillance.
Relation:	Oncotargets and Therapy, v.13, pp.14
Appears in Collections:	[Dept. of Senior Service and Health Management] Periodical Articles

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