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

• DOI: 10.1016/j.isci.2023.106076
• Publication Date: 2023-01-31T08:21:10Z
• Authors: C. Alicia Traughber; Gauravi M. Deshpande; Kalash Neupane; Nilam Bhandari; Mariam R. Khan; Megan R. McMullen; Shadi Swaidani; Emmanuel Opoku; Santoshi Muppala; Jonathan D. Smith; Laura E. Nagy; Kailash Gulshan
• Keywords: Lewis lung carcinoma; Tumor progression; AIM2

The activities of the NLRP3 and AIM2 inflammasomes Gasdermin D (GsdmD) are implicated in lung cancer pathophysiology but it's not clear if their contributions promote or retard progression. Using a metastatic Lewis carcinoma (LLC) cell model, we show that GsdmD knockout (GsdmD-/-) mice form significantly fewer foci lungs, exhibit markedly decreased metastasis, significant ∼50% increase median survival rate. cleaved forms IL-1β were detected tumor tissue, indicating inflammasome activity microenvironment (TME). Increased migration growth LLC cells was observed upon exposure to conditioned media derived from inflammasome-induced wild type, GsdmD-/-, macrophages. bone marrow transplantations, myeloid-specific contribution metastasis. Taken together, our data plays role