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The ?v?6 integrin in cancer cell-derived small extracellular vesicles enhances angiogenesis.

ABSTRACT: Prostate cancer (PrCa) cells crosstalk with the tumour microenvironment by releasing small extracellular vesicles (sEVs). sEVs, as well as large extracellular vesicles (LEVs), isolated via iodixanol density gradients from PrCa cell culture media, express the epithelial-specific ?v?6 integrin, which is known to be induced in cancer. In this study, we show sEV-mediated protein transfer of ?v?6 integrin to microvascular endothelial cells (human microvascular endothelial cells 1 - HMEC1) and demonstrate that de novo ?v?6 integrin expression is not caused by increased mRNA levels. Incubation of HMEC1 with sEVs isolated from PrCa PC3 cells that express the ?v?6 integrin results in a highly significant increase in the number of nodes, junctions and tubules. In contrast, incubation of HMEC1 with sEVs isolated from ?6 negative PC3 cells, generated by shRNA against ?6, results in a reduction in the number of nodes, junctions and tubules, a decrease in survivin levels and an increase in a negative regulator of angiogenesis, pSTAT1. Furthermore, treatment of HMEC1 with sEVs generated by CRISPR/Cas9-mediated down-regulation of ?6, causes up-regulation of pSTAT1. Overall, our findings suggest that ?v?6 integrin in cancer sEVs regulates angiogenesis during PrCa progression.

SUBMITTER: Krishn SR

PROVIDER: S-EPMC7301698 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The αvβ6 integrin in cancer cell-derived small extracellular vesicles enhances angiogenesis.

Krishn Shiv Ram SR Salem Israa I Quaglia Fabio F Naranjo Nicole M NM Agarwal Ekta E Liu Qin Q Sarker Srawasti S Kopenhaver Jessica J McCue Peter A PA Weinreb Paul H PH Violette Shelia M SM Altieri Dario C DC Languino Lucia R LR

Journal of extracellular vesicles 20200520 1

Prostate cancer (PrCa) cells crosstalk with the tumour microenvironment by releasing small extracellular vesicles (sEVs). sEVs, as well as large extracellular vesicles (LEVs), isolated via iodixanol density gradients from PrCa cell culture media, express the epithelial-specific αvβ6 integrin, which is known to be induced in cancer. In this study, we show sEV-mediated protein transfer of αvβ6 integrin to microvascular endothelial cells (human microvascular endothelial cells 1 - HMEC1) and demonst ...[more]

PMID: 32595914

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The ?v?6 integrin in cancer cell-derived small extracellular vesicles enhances angiogenesis.

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The αvβ6 integrin in cancer cell-derived small extracellular vesicles enhances angiogenesis.

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