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

First Author  Traughber CA Year  2023
Journal  iScience Volume  26
Issue  2 Pages  106076
PubMed ID  36844454 Mgi Jnum  J:334452
Mgi Id  MGI:7441575 Doi  10.1016/j.isci.2023.106076
Citation  Traughber CA, et al. (2023) Myeloid-cell-specific role of Gasdermin D in promoting lung cancer progression in mice. iScience 26(2):106076
abstractText  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 approximately 50% increase in median survival rate. The cleaved forms of GsdmD and IL-1beta 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.
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