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The β1 integrins, known to promote cancer progression, are abundant in extracellular vesicles (EVs). We investigated whether prostate cancer (PrCa) EVs affect anchorage-independent growth and whether β1 integrins are required for this effect. Specifically using a cell-line-based genetic rescue and an in vivo PrCa model, we show that gradient-purified small EVs (sEVs) from either cancer cells or blood from tumor-bearing TRAMP (transgenic adenocarcinoma of the mouse prostate) mice promote anchorage-independent growth of PrCa cells. In contrast, sEVs from cultured PrCa cells harboring a short hairpin RNA to β1, from wild-type mice or from TRAMP mice carrying a β1 conditional ablation in the prostatic epithelium (β1), do not. We find that sEVs, from cancer cells or TRAMP blood, are functional and co-express β1 and sEV markers; in contrast, sEVs from β1/TRAMP or wild-type mice lack β1 and sEV markers. Our results demonstrate that β1 integrins in tumor-cell-derived sEVs are required for stimulation of anchorage-independent growth.
This article was published in the following journal.
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Membrane limited structures derived from cell membranes and cytoplasmic material, and released into EXTRACELLULAR SPACE. They circulate through the EXTRACELLULAR FLUID and through the peripheral blood in the MICROVASCULATURE where cells, much larger, cannot, thereby affecting a variety of intercellular communication processes.
An anchoring junction of the cell to a non-cellular substrate, similar in morphology to halves of DESMOSOMES. They are composed of specialized areas of the plasma membrane where INTERMEDIATE FILAMENTS bind on the cytoplasmic face to the transmembrane linkers, INTEGRINS, via intracellular attachment proteins, while the extracellular domain of the integrins binds to EXTRACELLULAR MATRIX PROTEINS.
Vesicles derived from the GOLGI APPARATUS containing material to be released at the cell surface.
Vesicles secreted from MULTIVESICULAR BODIES into the extracellular environment when the multivesicular bodies fuse with the PLASMA MEMBRANE. Multivesicular bodies are formed from ENDOSOMES when they accumulate vesicles (sometimes referred to as "intraluminal vesicles") from inward budding of the endosome membrane.
An anchoring junction of the cell to a non-cellular substrate. It is composed of a specialized area of the plasma membrane where bundles of MICROFILAMENTS terminate and attach to the transmembrane linkers, INTEGRINS, which in turn attach through their extracellular domains to EXTRACELLULAR MATRIX PROTEINS.
Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...