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Education of tumour-associated macrophages by the tumour matrisome inhibits immune surveillance

ABSTRACT: Education of tumour-associated macrophages by the tumour matrisome inhibits immune surveillance

PROVIDER: PRJNA772736 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16490632_1.fastq.gz	Fastqsanger.gz
	SRR16490632_2.fastq.gz	Fastqsanger.gz
	SRR16490633_1.fastq.gz	Fastqsanger.gz
	SRR16490633_2.fastq.gz	Fastqsanger.gz
	SRR16490634_1.fastq.gz	Fastqsanger.gz

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Education of tumour-associated macrophages by the tumour matrisome inhibits immune surveillance

Project description:Metastatic ovarian tissues represent a complex tumour microenviroment. We analysed the tumour matrisome and immune cell environment in 39 metastatic ovarian tissues. We developed a disease score system, which positively correlated with the tumour matrisome. A distinct matrisome signature was identfied with increasing disease. Immune abundance and phenotype positively correaletd with tumour matrisome components. We developed a decellularised tissue model using metastatic ovarian omental tissues that maintained ECM protein content and architecture and cultured human blood-derived macrophages derived from four different donors. Monocytes cultured on high diseased tissues differerntiated into a distinct macrophage population, different from uninvovled (low disease) samples. Tumour ECM cultured macrophages had pro-tumorgenic phenotype and function.

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Project description:The composition and remodelling of the extracellular matrix (ECM) are important factors in the development and progression of cancers, and the ECM is implicated in promoting tumour growth and restricting anti-tumour therapies through multiple mechanisms. The characterisation of differences in ECM composition between normal and diseased tissues may aid in identifying novel diagnostic markers, prognostic indicators and therapeutic targets for drug development. Using tissue from non-small cell lung cancer (NSCLC) patients undergoing curative intent surgery, we characterised quantitative tumour-specific ECM proteome signatures by mass spectrometry, identifying 161 matrisome proteins differentially regulated between tumour tissue and nearby non-malignant lung tissue. We defined a collagen hydroxylation functional protein network that is enriched in the lung tumour microenvironment. We validated two novel putative extracellular markers of NSCLC, the collagen cross-linking enzyme peroxidasin and a disintegrin and metalloproteinase with thrombospondin motifs 16 (ADAMTS16), for discrimination of malignant and non-malignant lung tissue. These proteins were up-regulated in lung tumour samples, and high PXDN and ADAMTS16 gene expression was associated with shorter survival of lung adenocarcinoma and squamous cell carcinoma patients, respectively. These data reveal tumour matrisome signatures in human NSCLC.

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The zingerone analog, acetyl zingerone, bolsters matrisome synthesis, inhibits MMPs, and represses IL-17A target gene expression

Project description:The zingerone analog, acetyl zingerone, bolsters matrisome synthesis, inhibits MMPs, and represses IL-17A target gene expression

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