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来自同一患者的人胰腺癌细胞之间通过细胞外囊泡的细胞间通讯。

Cell‑to‑cell communication via extracellular vesicles among human pancreatic cancer cells derived from the same patient.

机构信息

Department of Bioscience and Laboratory Medicine, Graduate School of Health Sciences, Hirosaki University, Hirosaki, Aomori 036‑8564, Japan.

Department of Medical Technology, Graduate School of Health Sciences, Hirosaki University, Hirosaki, Aomori 036‑8564, Japan.

出版信息

Mol Med Rep. 2018 Oct;18(4):3989-3996. doi: 10.3892/mmr.2018.9376. Epub 2018 Aug 9.

Abstract

Despite existing multimodal therapies, pancreatic cancer exhibits high metastatic capability and poor prognosis. Extracellular vesicles (EVs) are nanoparticles comprising lipid bilayers and various other components, such as protein and nucleic acids, derived from secreted cells. Recent research has demonstrated the involvement of EVs released from cancer cells in the metastasis of cancer cells to distant organs. However, the effects of EVs released from pancreatic cancer cells on other pancreatic cancer cells in a tumor microenvironment remain unclear. The present study aimed to elucidate that EVs released from PK‑45H pancreatic cancer cells are taken up by PK‑45P pancreatic cancer cells derived from the same patient through dynamin‑related endocytosis. Additionally, EVs released from PK‑45H cells augment the phosphorylation of classical mitogen‑activated protein kinase (MAPK) pathways in PK‑45P cells. The uptake of EVs released from PK‑45H cells by PK‑45P cells stimulates cell migration through the classical MAPK‑dependent pathway, suggesting that EVs released from one pancreatic cancer cell are taken up by other surrounding pancreatic cancer cells and could be critical inducers of cancer metastasis in the tumor microenvironment.

摘要

尽管存在多种模式的治疗方法,但胰腺癌仍具有高度的转移性和较差的预后。细胞外囊泡(EVs)是由脂质双层和各种其他成分(如蛋白质和核酸)组成的纳米颗粒,来源于分泌细胞。最近的研究表明,癌细胞释放的 EVs 参与了癌细胞向远处器官的转移。然而,肿瘤微环境中胰腺癌细胞释放的 EVs 对其他胰腺癌细胞的影响尚不清楚。本研究旨在阐明来自同一位患者的 PK-45H 胰腺癌细胞释放的 EVs 通过与胞吞作用相关的动力蛋白相关内吞作用被 PK-45P 胰腺癌细胞摄取。此外,来自 PK-45H 细胞的 EVs 的释放增加了 PK-45P 细胞中经典丝裂原活化蛋白激酶(MAPK)途径的磷酸化。PK-45H 细胞释放的 EVs 被 PK-45P 细胞摄取刺激了细胞迁移通过经典 MAPK 依赖途径,这表明来自一个胰腺癌细胞的 EVs 被其他周围的胰腺癌细胞摄取,并可能是肿瘤微环境中癌症转移的关键诱导因素。

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