IL-9 Abrogates the Metastatic Potential of Breast Cancer by Controlling Extracellular Matrix Remodeling and Cellular Contractility
Copyright © 2021 by The American Association of Immunologists, Inc..
IL-9 is produced by Th9 cells and is classically known as a growth-promoting cytokine. Although protumorigenic functions of IL-9 are described in T cell lymphoma, recently, we and others have reported anti-tumor activities of IL-9 in melanoma mediated by mast cells and CD8+ T cells. However, involvement of IL-9 in invasive breast and cervical cancer remains unexplored. In this study, we demonstrate IL-9-dependent inhibition of metastasis of both human breast (MDA-MB-231 and MCF-7) and cervical (HeLa) tumor cells in physiological three-dimensional invasion assays. To dissect underlying mechanisms of IL-9-mediated suppression of invasion, we analyzed IL-9-dependent pathways of cancer cell metastasis, including proteolysis, contractility, and focal adhesion dynamics. IL-9 markedly blocked tumor cell-collagen degradation, highlighting the effects of IL-9 on extracellular matrix remodeling. Moreover, IL-9 significantly reduced phosphorylation of myosin L chain and resultant actomyosin contractility and also increased focal adhesion formation. Finally, IL-9 suppressed IL-17- and IFN-γ-induced metastasis of both human breast (MDA-MB-231) and cervical (HeLa) cancer cells. In conclusion, IL-9 inhibits the metastatic potential of breast and cervical cancer cells by controlling extracellular matrix remodeling and cellular contractility.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:206 |
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| Enthalten in: |
Journal of immunology (Baltimore, Md. : 1950) - 206(2021), 11 vom: 01. Juni, Seite 2740-2752 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Das, Sreya [VerfasserIn] |
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| Links: |
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| Themen: |
IL9 protein, human |
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| Anmerkungen: |
Date Completed 29.09.2021 Date Revised 29.09.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4049/jimmunol.2000383 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM325703841 |
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| 520 | |a Copyright © 2021 by The American Association of Immunologists, Inc. | ||
| 520 | |a IL-9 is produced by Th9 cells and is classically known as a growth-promoting cytokine. Although protumorigenic functions of IL-9 are described in T cell lymphoma, recently, we and others have reported anti-tumor activities of IL-9 in melanoma mediated by mast cells and CD8+ T cells. However, involvement of IL-9 in invasive breast and cervical cancer remains unexplored. In this study, we demonstrate IL-9-dependent inhibition of metastasis of both human breast (MDA-MB-231 and MCF-7) and cervical (HeLa) tumor cells in physiological three-dimensional invasion assays. To dissect underlying mechanisms of IL-9-mediated suppression of invasion, we analyzed IL-9-dependent pathways of cancer cell metastasis, including proteolysis, contractility, and focal adhesion dynamics. IL-9 markedly blocked tumor cell-collagen degradation, highlighting the effects of IL-9 on extracellular matrix remodeling. Moreover, IL-9 significantly reduced phosphorylation of myosin L chain and resultant actomyosin contractility and also increased focal adhesion formation. Finally, IL-9 suppressed IL-17- and IFN-γ-induced metastasis of both human breast (MDA-MB-231) and cervical (HeLa) cancer cells. In conclusion, IL-9 inhibits the metastatic potential of breast and cervical cancer cells by controlling extracellular matrix remodeling and cellular contractility | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a Interleukin-9 |2 NLM | |
| 700 | 1 | |a Surve, Vishakha |e verfasserin |4 aut | |
| 700 | 1 | |a Marathe, Soumitra |e verfasserin |4 aut | |
| 700 | 1 | |a Wad, Siddhi |e verfasserin |4 aut | |
| 700 | 1 | |a Karulkar, Atharva |e verfasserin |4 aut | |
| 700 | 1 | |a Srinivasan, Srisathya |e verfasserin |4 aut | |
| 700 | 1 | |a Dwivedi, Alka |e verfasserin |4 aut | |
| 700 | 1 | |a Barthel, Steven R |e verfasserin |4 aut | |
| 700 | 1 | |a Purwar, Rahul |e verfasserin |4 aut | |
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