Tumor extracellular vesicles drive metastasis (it's a long way from home)


Posted: 2021-11-11 20:00:00
FIGURE 1 Tumor extracellular vesicles prime premetastatic niches. The journey of EVs from the primary… FIGURE 1 Tumor extracellular vesicles prime premetastatic niches. The journey of EVs from the primary tumor to the future metastatic organ is a multistep process initiated with the secretion of tumor‐derived EVs and other tumor‐derived soluble factors (TDSF) from the primary tumor. 1. Upon secretion, tumor‐derived EVs leave the primary tumor and travel through the blood and lymphatic circulation, where they interact with blood components like neutrophils, endothelial cells, platelets, low‐density lipoproteins (LDL), and other immune cells. These interactions affect blood homeostasis, enhance the uptake of tumor EVs by distinct recipient cells, and could induce endothelial permeabilization, thereby promoting the formation of premetastatic niche (PMN). 2. Tumor EVs are further taken up by patrolling monocytes and endothelial cells and some of the tumor EVs pass through the impermeable endothelial cells within the tissue by transcytosis. Uptake of tumor EVs by these recipient cells can directly impact the PMN formation. Inset shows a magnified tumor EV, that are encapsulated by a lipid bilayer, containing various biomolecules such as DNA, RNA, proteins as well glycans, specialized receptors at their surface (CD47, CD9, and CD63), and several adhesion proteins such as integrins and MCAM. 3. Key features of the PMN. Highlighted are the key features of the PMN and their associated tumor EV cargos that actively contribute to efficient PMN formation. Upon internalization by distinct recipient cells, tumor EVs deliver their cargo, induce phenotypic changes in them, thereby promoting ECM remodeling, reprogramming cell metabolism, inducing immunomodulation, angiogenesis and vascular permeability, lymphangiogenesis, and also triggering pro‐inflammatory molecules. All these salient features eventually promote PMN formation. 4. Following the PMN formation, circulating tumor cells (CTCs) eventually reach the PMN and colonize in the new tissue, leading to metastasis. Highlighted in the far left, is the human women model demonstrating organotrophic metastasis, where primary breast tumor‐secreted EVs prime PMN at distant organs such as lungs, brain, liver, and bone. Created with BioRender.com

参考サイト PubMed: exsome



バイオクイックニュース日本語版:エクソソーム特集

バイオクイックニュース日本語版
8月 01, 2019 バイオアソシエイツ

エクソソームが脳細胞と回路の形成に深い役割を果たし、発達性脳障害の治療と診断に寄与する可能性をスクリプス研究所が示唆。

ジェット機の下から荷降ろしされるたくさん詰め込まれたスーツケースのように、 エクソソーム と呼ばれる生物学的小包は、体内のすべての細胞から継続的に展開され、これらを送り出すことによって細胞はタンパク質および遺伝物質を介して互いに通信をする。 単に細胞の「ゴミ」の微小な袋であると考えられていたエクソソームは、今や我々の健康にとって非常に重要なものであると理解されている。 近年の研究では、癌やアルツハイマー病などの神経変性疾患の蔓延に関連した分子を輸送することを示している。…

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