徳島大学 教育・研究者情報データベース(EDB)

1. (英) Chen Shuhai / (日) 陳 述海 / (読) ちん じゅつかい

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2. 森根 裕二([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.外科系.消化器・移植外科学]/[徳島大学.病院.診療科.外科.消化器・移植外科])

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3. 徳田 和憲([徳島大学.病院.診療科.第一外科])

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4. 山田 眞一郎([徳島大学.病院.診療科.外科.消化器・移植外科])

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5. 齋藤 裕([徳島大学.病院.診療科.外科.消化器・移植外科])

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6. 西 正暁([徳島大学.大学院医歯薬学研究部.医学域.連携研究部門(医学域).寄附講座系(医学域).実践地域診療・医科学])

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7. 池本 哲也([徳島大学.病院.中央診療施設等.安全管理部]/[徳島大学.病院.診療科.外科.消化器・移植外科])

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8. 島田 光生

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(英) Cancerssociated fibroblastnduced M2olarized macrophages promote hepatocellular carcinoma progression via the plasminogen activator inhibitor 1 pathway.

(英) Targeting the tumor stroma is an important strategy in cancer treatment. Cancerssociated fibroblasts (CAFs) and tumorssociated macrophages (TAMs) are two main components in the tumor microenvironment (TME) in hepatocellular carcinoma (HCC), which can promote tumor progression. Plasminogen activator inhibitor 1 (PAI 1) upregulation in HCC is predictive of unfavorable tumor behavior and prognosis. However, the crosstalk between cancer cells, TAMs and CAFs, and the functions of PAI 1 in HCC remain to be fully investigated. In the present study, macrophage polarization and key paracrine factors were assessed during their interactions with CAFs and cancer cells. Cell proliferation, wound healing and Transwell and Matrigel assays were used to investigate the malignant behavior of HCC cells . It was found that cancer cells and CAFs induced the M2 polarization of TAMs by upregulating the mRNA expression levels of CD163 and CD206, and downregulating IL 6 mRNA expression and secretion in the macrophages. Both TAMs derived from cancer cells and CAFs promoted HCC cell proliferation and invasion. Furthermore, PAI 1 expression was upregulated in TAMs after being stimulated with CAFonditioned medium and promoted the malignant behavior of the HCC cells by mediating epithelialesenchymal transition. CAFs were the main producer of C motif chemokine ligand 12 (CXCL12) in the TME and CXCL12 contributed to the induction of PAI 1 secretion in TAMs. In conclusion, the results of the present study suggested that CAFs promoted the M2 polarization of macrophages and induced PAI 1 secretion via CXCL12. Furthermore, it was found that PAI 1 produced by the TAMs enhanced the malignant behavior of the HCC cells. Therefore, these factors may be targets for inhibiting the crosstalk between tumor cells, CAFs and TAMs.

1. (英) Cancer-Associated Fibroblasts
2. (英) Carcinoma, Hepatocellular
3. (英) Cell Communication
4. (英) Cell Line, Tumor
5. (英) Cell Movement
6. (英) Cell Polarity
7. (英) Cell Proliferation
8. (英) Coculture Techniques
9. (英) Disease Progression
10. (英) Gene Expression Regulation, Neoplastic
11. (英) Humans
12. (英) Liver Neoplasms
13. (英) Macrophage Activation
14. (英) Plasminogen Activator Inhibitor 1
15. (英) Prognosis
16. (英) Signal Transduction
17. (英) THP-1 Cells
18. (英) Tumor Microenvironment
19. (英) Tumor-Associated Macrophages
20. (英) Up-Regulation

1. (英) Article.ELocationID: 10.3892/ijo.2021.5239

2. (英) Article.ELocationID: 59

3. (英) Article.PublicationTypeList.PublicationType: Journal Article

4. (英) KeywordList.Keyword: cancerssociated fibroblasts

5. (英) KeywordList.Keyword: epithelialesenchymal transition

6. (英) KeywordList.Keyword: hepatocellular carcinoma

7. (英) KeywordList.Keyword: plasminogen activator inhibitor 1

8. (英) KeywordList.Keyword: tumorssociated macrophages