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Tumour-derived Extracellular Vesicle and Particle Reprogramming of Interstitial Macrophages in the Lung Pre-Metastatic Niche Enhances Vascular Permeability and Metastatic Potential

ABSTRACT: Tumour-derived Extracellular Vesicle and Particle Reprogramming of Interstitial Macrophages in the Lung Pre-Metastatic Niche Enhances Vascular Permeability and Metastatic Potential

PROVIDER: PRJNA1085343 | ENA |

REPOSITORIES: ENA

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Cancer EVP Uptake in Lung Interstitial Macrophages Enhances Vascular Permeability and Metastatic Potential (in vivo)

Project description:Enhanced vascular permeability in the pre-metastatic niche facilitates tumor cell extravasation and metastasis. Extracellular vesicles and particles (EVPs) are pivotal mediators of cancer progression, including induction of vascular permeability. We identify a novel mechanism whereby melanoma and osteosarcoma EVPs (B16F10 and K7M2) enhance endothelial cell permeability, tumor extravasation and lung metastasis.In contrast, EVPs from breast tumors (4T1 and 67NR) elicited only mild vascular permeability, tumor cell extravasation, and metastasis. EVP induced vascular leakiness is observed within 48h following tumor implantation and as early one hour following direct injection of the B16F10 or K7M2 derived EVPs in non-tumor bearing mice. Rather than acting directly on endothelial cells, EVPs activated interstitial macrophages (IMs) anddepletion of IM with a CSF1R antibody significantly reduced vascular leakiness and metastatic potential.Subsequent activation of JAK/STAT signaling in IMs induces IL-6 secretion which in turn induces endothelial permeability.B16F10 and K7M2 EVPs highly expressed ITGα5 compared to breast tumors, and knock down ofintegrin-α5impairs IM signaling, vascular permeability and metastasis. Furthermore, in patients Il-6 expression is elevated in tumor-adjacent IMs compared to distant tissues. Our findings identify a key role for IMs in mediating tumor type-specific EVP-driven vascular permeability and metastasis, offering promising targets for therapeutic intervention.

2024-06-26 | GSE261138 | GEO

Cancer EVP Uptake in Lung Interstitial Macrophages Enhances Vascular Permeability and Metastatic Potential (in vitro)

Project description:Enhanced vascular permeability in the pre-metastatic niche facilitates tumor cell extravasation and metastasis. Extracellular vesicles and particles (EVPs) are pivotal mediators of cancer progression, including induction of vascular permeability. We identify a novel mechanism whereby melanoma and osteosarcoma EVPs (B16F10 and K7M2) enhance endothelial cell permeability, tumor extravasation and lung metastasis.In contrast, EVPs from breast tumors (4T1 and 67NR) elicited only mild vascular permeability, tumor cell extravasation, and metastasis. EVP induced vascular leakiness is observed within 48h following tumor implantation and as early one hour following direct injection of the B16F10 or K7M2 derived EVPs in non-tumor bearing mice. Rather than acting directly on endothelial cells, EVPs activated interstitial macrophages (IMs) anddepletion of IM with a CSF1R antibody significantly reduced vascular leakiness and metastatic potential.Subsequent activation of JAK/STAT signaling in IMs induces IL-6 secretion which in turn induces endothelial permeability.B16F10 and K7M2 EVPs highly expressed integrin-α5 compared to breast tumors, and knock down ofITGα5impairs IM signaling, vascular permeability and metastasis. Furthermore, in patients Il-6 expression is elevated in tumor-adjacent IMs compared to distant tissues. Our findings identify a key role for IMs in mediating tumor type-specific EVP-driven vascular permeability and metastasis, offering promising targets for therapeutic intervention.

2024-06-26 | GSE261137 | GEO

Cancer EVP Uptake in Lung Interstitial Macrophages Enhances Vascular Permeability and Metastatic Potential (in vivo)

Project description:Cancer EVP Uptake in Lung Interstitial Macrophages Enhances Vascular Permeability and Metastatic Potential (in vivo)

| PRJNA1085348 | ENA

Cancer EVP Uptake in Lung Interstitial Macrophages Enhances Vascular Permeability and Metastatic Potential (in vitro)

Project description:Cancer EVP Uptake in Lung Interstitial Macrophages Enhances Vascular Permeability and Metastatic Potential (in vitro)

| PRJNA1085337 | ENA

Extracellular Vesicle and Particle miRNAs in Maternal Plasma

Project description:Extracellular Vesicle and Particle miRNAs in Maternal Plasma

| PRJNA925502 | ENA

Extracellular Vesicle and Particle miRNAs in Human Milk

Project description:Extracellular Vesicle and Particle miRNAs in Human Milk

| PRJNA925503 | ENA

Tumour-derived Extracellular Vesicle and Particle Reprogramming of Interstitial Macrophages in the Lung Pre-Metastatic Niche Enhances Vascular Permeability and Metastatic Potential

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-06-26 | GSE261139 | GEO

Deep sequencing identified serum extracellular vesicle delivered miR-181a-5p as an indicator for bone-metastatic prostate cancer (microarray)

Project description:Purpose: The goals of this study are to compare the serum extracellular vesicle (EV) delivered miRNA levels of patients with bone-metastatic prostate cancer (PCa), non-bone -metastatic PCa and benign prostatic hyperplasia (BPH), and to identify EV-delivered microRNAs in patient’s serum as indicators for bone-metastatic PCa. Methods:Serum extracellular vesicle delivered miRNA profiles of patients with bone-metastatic PCa or non-bone -metastatic PCa or BPH were generated by miRNA chip array, using Agilent-070156 Human_miRNA_V21.0_Microarray plateform. Results: Differential analysis showed the expressions of 27 EV delivered miRNAs were significantly different between serum of patients with bone-metastatic PCa and non-bone-metastatic PCa with a p value <0.05. the expressions of 5 EV delivered miRNAs were confirmed with qRT–PCR. Conclusions: Serum EV-delivered miR-181a-5p is a promising diagnostic biomarker for bone-metastatic PCa.

2020-01-31 | GSE134266 | GEO

Urinary extracellular vesicle microRNA profiling for detection in patients with interstitial cystitis

Project description:Urinary extracellular vesicle microRNA profiling for detection in patients with interstitial cystitis

| PRJNA803480 | ENA

Deep sequencing identified serum extracellular vesicle delivered miR-181a-5p as an indicator for bone-metastatic prostate cancer

Project description:Purpose: The goals of this study are to compare the serum extracellular vesicle (EV) delivered miRNA levels of patients with bone-metastatic prostate cancer (PCa), non-bone -metastatic PCa and benign prostatic hyperplasia (BPH), and to identify EV-delivered microRNAs in patient’s serum as indicators for bone-metastatic PCa. Methods:Serum extracellular vesicle delivered miRNA profiles of patients with bone-metastatic PCa or non-bone -metastatic PCa or BPH were generated by deep sequencing, using Illumina HiSeqTM 2500 platform Results: Using an optimized data analysis method, we mapped about 17 million sequence reads per sample. Differential analysis showed the expressions of 35 EV delivered miRNAs were significantly different between serum of patients with PCa and BPH, with a p value <0.05. the expressions of 5 EV delivered miRNAs were confirmed with qRT–PCR. Conclusions: Serum EV-delivered miR-181a-5p is a promising diagnostic biomarker for bone-metastatic PCa.

2020-01-31 | GSE134205 | GEO

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