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Clearance of a senescent macrophage-enriched niche ameliorates tumorigenesis in KRAS-driven murine lung cancer models

ABSTRACT: Understanding the important role of the tumour microenvironment on tumour initiation and progression is vital for a comprehensive understanding of cancer biology to design effective treatment strategies. Cellular senescence, while traditionally thought of as a cell autonomous tumour-suppressive response to potentially oncogenic insults, is now appreciated to have paracrine tumour promoting roles. We demonstrate a pro-tumourigenic effect of senescent microenvironmental cells on mouse lung tumour progression. To better understand the characteristics of these pro-tumourigenic senescent cells in the tumour microenvironment, we compare putatively senescent cells (reported by mCherry-expression) and non-senescent cells (mCherry-negative cells) from the lung microenvironment of mice induced to form lung tumours by oncogenic KrasG12D-expression in the lung epithelium. Putatively senescent cells are isolated by FACS, based on mCherry-expression which is expressed under the control of the Cdkn2a (p16) locus using a novel genetically engineered allele (p16FDR/+), along with their non-senescent counterparts for comparison by single cell RNA-sequencing.

ORGANISM(S): Mus musculus

PROVIDER: GSE203447 | GEO | 2023/06/14

REPOSITORIES: GEO

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Clearance of senescent macrophages ameliorates tumorigenesis in KRAS-driven lung cancer

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