Myeloid-cell-specific role of Gasdermin D in promoting lung cancer progression in mice.

Autor:	Traughber CA; Center for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH 44115, USA.; Department of Biology, Geology, and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USA.; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA., Deshpande GM; Digital Imaging Core, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA., Neupane K; Center for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH 44115, USA.; Department of Biology, Geology, and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USA., Bhandari N; Center for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH 44115, USA.; Department of Biology, Geology, and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USA., Khan MR; Center for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH 44115, USA.; Department of Biology, Geology, and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USA., McMullen MR; Departments of Inflammation and Immunity and Gastroenterology/Hepatology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.; Northern Ohio Alcohol Center, Cleveland Clinic, Cleveland, OH 44195, USA., Swaidani S; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA., Opoku E; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA., Muppala S; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA., Smith JD; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA., Nagy LE; Departments of Inflammation and Immunity and Gastroenterology/Hepatology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.; Northern Ohio Alcohol Center, Cleveland Clinic, Cleveland, OH 44195, USA., Gulshan K; Center for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH 44115, USA.; Department of Biology, Geology, and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USA.; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2023 Jan 31; Vol. 26 (2), pp. 106076. Date of Electronic Publication: 2023 Jan 31 (Print Publication: 2023).
DOI:	10.1016/j.isci.2023.106076
Abstrakt:	The activities of the NLRP3 and AIM2 inflammasomes and Gasdermin D (GsdmD) are implicated in lung cancer pathophysiology but it's not clear if their contributions promote or retard lung cancer progression. Using a metastatic Lewis lung carcinoma (LLC) cell model, we show that GsdmD knockout (GsdmD -/- ) mice form significantly fewer cancer foci in lungs, exhibit markedly decreased lung cancer metastasis, and show a significant ∼50% increase in median survival rate. The cleaved forms of GsdmD and IL-1β were detected in lung tumor tissue, indicating inflammasome activity in lung tumor microenvironment (TME). Increased migration and growth of LLC cells was observed upon exposure to the conditioned media derived from inflammasome-induced wild type, but not the GsdmD -/- , macrophages. Using bone marrow transplantations, we show a myeloid-specific contribution of GsdmD in lung cancer metastasis. Taken together, our data show that GsdmD plays a myeloid-specific role in lung cancer progression. Competing Interests: The authors declare no competing interests. (© 2023 The Author(s).)
Databáze:	MEDLINE
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