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肥大细胞是Myc诱导的胰岛肿瘤血管生成和宏观扩张所必需的。

Mast cells are required for angiogenesis and macroscopic expansion of Myc-induced pancreatic islet tumors.

作者信息

Soucek Laura, Lawlor Elizabeth R, Soto Darya, Shchors Ksenya, Swigart Lamorna Brown, Evan Gerard I

机构信息

Cancer Research Institute and Department of Pathology, University of California San Francisco, 2340 Sutter Street, San Francisco, California 94143-0875, USA.

出版信息

Nat Med. 2007 Oct;13(10):1211-8. doi: 10.1038/nm1649. Epub 2007 Sep 30.

Abstract

An association between inflammation and cancer has long been recognized, but the cause and effect relationship linking the two remains unclear. Myc is a pleiotropic transcription factor that is overexpressed in many human cancers and instructs many extracellular aspects of the tumor tissue phenotype, including remodeling of tumor stroma and angiogenesis. Here we show in a beta-cell tumor model that activation of Myc in vivo triggers rapid recruitment of mast cells to the tumor site-a recruitment that is absolutely required for macroscopic tumor expansion. In addition, treatment of established beta-cell tumors with a mast cell inhibitor rapidly triggers hypoxia and cell death of tumor and endothelial cells. Inhibitors of mast cell function may therefore prove therapeutically useful in restraining expansion and survival of pancreatic and other cancers.

摘要

炎症与癌症之间的关联早已为人所知,但两者之间的因果关系仍不清楚。Myc是一种多效性转录因子,在许多人类癌症中过度表达,并指导肿瘤组织表型的许多细胞外方面,包括肿瘤基质重塑和血管生成。在这里,我们在β细胞肿瘤模型中表明,体内Myc的激活会触发肥大细胞迅速募集到肿瘤部位——这一募集对于宏观肿瘤扩展是绝对必需的。此外,用肥大细胞抑制剂治疗已建立的β细胞肿瘤会迅速引发肿瘤和内皮细胞的缺氧和细胞死亡。因此,肥大细胞功能抑制剂可能在抑制胰腺癌和其他癌症的扩展和存活方面具有治疗作用。

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