1. IL-9 Abrogates the Metastatic Potential of Breast Cancer by Controlling Extracellular Matrix Remodeling and Cellular Contractility
- Author
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Atharva Karulkar, Rahul Purwar, S. Srinivasan, Steven R. Barthel, Siddhi Wad, Sreya Das, Soumitra Marathe, Alka Dwivedi, and Vishakha Surve
- Subjects
biology ,Chemistry ,medicine.medical_treatment ,Immunology ,Interleukin-9 ,Breast Neoplasms ,biology.organism_classification ,medicine.disease ,Metastasis ,Extracellular Matrix ,Extracellular matrix ,HeLa ,Contractility ,Focal adhesion ,Cytokine ,Breast cancer ,Cell Movement ,Cancer cell ,Cancer research ,medicine ,Cell Adhesion ,Tumor Cells, Cultured ,Immunology and Allergy ,Humans ,Female - Abstract
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.
- Published
- 2020