小柯机器人

美国德克萨斯大学西南医学中心Sean J. Morrison研究组取得最新进展。他们发现淋巴可保护转移性黑色素瘤细胞免于肥大症。 这一研究成果发表在2020年8月19日出版的国际学术期刊《自然》杂志上。

他们显示淋巴中的黑素瘤细胞比血液中的黑素瘤细胞经历较少的氧化应激并形成更多的转移。源自患者的黑色素瘤免疫功能低下的小鼠，具有小鼠黑色素瘤的免疫活性小鼠的肿瘤引流淋巴中每微升黑色素瘤细胞多于肿瘤引流血液。通过血液转移的细胞更依赖于肥大症抑制剂GPX4，而通过淋巴转移的细胞不会。静脉内但非淋巴内注射后，用化学类肥大症抑制剂预处理的细胞比未处理的细胞形成更多的转移。

他们观察到淋巴液和血浆之间存在多种差异，可能导致氧化应激降低和淋巴受精症，包括谷胱甘肽和油酸水平升高，淋巴中游离铁减少。油酸以Acsl3依赖性方式保护黑素瘤细胞免于肥大症，并增加其形成转移性肿瘤的能力。与来自皮下肿瘤的黑色素瘤细胞相比，静脉注射后来自淋巴结的黑色素瘤细胞对肥大症更有抵抗力，并形成更多的转移灶。因此，暴露于淋巴环境可保护黑素瘤细胞免于肥大症，并增加其在随后通过血液转移的过程中存活的能力。

据了解，癌细胞（包括黑素瘤细胞），通常会通过淋巴系统局部转移，然后通过血液全身转移。但是，其原因尚不清楚。

附：英文原文

Title: Lymph protects metastasizing melanoma cells from ferroptosis

Author: Jessalyn M. Ubellacker, Alpaslan Tasdogan, Vijayashree Ramesh, Bo Shen, Evann C. Mitchell, Misty S. Martin-Sandoval, Zhimin Gu, Michael L. McCormick, Alison B. Durham, Douglas R. Spitz, Zhiyu Zhao, Thomas P. Mathews, Sean J. Morrison

Issue&Volume: 2020-08-19

Abstract: Cancer cells, including melanoma cells, often metastasize regionally through the lymphatic system before metastasizing systemically through the blood1–4; however, the reason for this is unclear. Here we show that melanoma cells in lymph experience less oxidative stress and form more metastases than melanoma cells in blood. Immunocompromised mice with melanomas derived from patients, and immunocompetent mice with mouse melanomas, had more melanoma cells per microlitre in tumour-draining lymph than in tumour-draining blood. Cells that metastasized through blood, but not those that metastasized through lymph, became dependent on the ferroptosis inhibitor GPX4. Cells that were pretreated with chemical ferroptosis inhibitors formed more metastases than untreated cells after intravenous, but not intralymphatic, injection. We observed multiple differences between lymph fluid and blood plasma that may contribute to decreased oxidative stress and ferroptosis in lymph, including higher levels of glutathione and oleic acid and less free iron in lymph. Oleic acid protected melanoma cells from ferroptosis in an Acsl3-dependent manner and increased their capacity to form metastatic tumours. Melanoma cells from lymph nodes were more resistant to ferroptosis and formed more metastases after intravenous injection than did melanoma cells from subcutaneous tumours. Exposure to the lymphatic environment thus protects melanoma cells from ferroptosis and increases their ability to survive during subsequent metastasis through the blood. Melanoma cells undergo less oxidative stress and less ferroptosis in lymph than in blood, owing to higher levels of oleic acid in lymph, and thus exposure to the lymphatic environment increases subsequent metastasis through blood.

DOI: 10.1038/s41586-020-2623-z

Source: https://www.nature.com/articles/s41586-020-2623-z

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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