2025年4月24日出版的《癌细胞》杂志发表了曼彻斯特大学Amaya Virós研究小组的最新成果，他们揭示了基质脂质种类决定黑色素瘤的转移和趋向性。

研究团队发现来自年轻皮下脂肪细胞的丰富基质脂质，包括磷脂酰胆碱，被黑色素瘤细胞吸收，在那里它们上调黑色素瘤PI3K-AKT信号，脂肪酸氧化，氧化磷酸化（OXPHOS）导致氧化应激，导致转移负担减少。高OXPHOS黑色素瘤细胞主要分布于肺和脑；用抗氧化剂减少氧化应激，使嗜性从肺转移到肝。相比之下，老年TME提供的总脂质较少，但神经酰胺丰富，导致OXPHOS降低和高转移负担。黑色素瘤细胞摄取老化的TME神经酰胺，激活S1P-STAT3-IL-6信号轴，促进肝向性。在年轻TME中抑制OXPHOS或在老年TME中阻断IL-6受体可降低脂质可用性施加的年龄特异性转移模式。

研究人员表示，癌细胞适应肿瘤微环境（TME）中的信号，但影响转移和趋向性的TME信号仍不完全清楚。

附：英文原文

Title: Stromal lipid species dictate melanoma metastasis and tropism

Author: Shilpa Gurung, Timothy Budden, Karthik Mallela, Benjamin Jenkins, Alex von Kriegsheim, Esperanza Manrique, David Millán-Esteban, Isabel Romero-Camarero, Fabio Amaral, Sarah Craig, Pedro Durao, Joanna Pozniak, Laura Stennett, Duncan Smith, Garry Ashton, Alex Baker, Kang Zeng, Gilbert Fruhwirth, Victoria Sanz-Moreno, Jair Marques, Albert Koulman, Jean-Christophe Marine, Tim C.P. Somervaille, Luisa Motta, Caroline Gaudy-Marqueste, Eduardo Nagore, Amaya Virós

Issue&Volume: 2025-04-24

Abstract: Cancer cells adapt to signals in the tumor microenvironment (TME), but the TME cues that impact metastasis and tropism are still incompletely understood. We show that abundant stromal lipids from young subcutaneous adipocytes, including phosphatidylcholines, are taken up by melanoma cells, where they upregulate melanoma PI3K-AKT signaling, fatty acid oxidation, oxidative phosphorylation (OXPHOS) leading to oxidative stress, resulting in decreased metastatic burden. High OXPHOS melanoma cells predominantly seed the lung and brain; decreasing oxidative stress with antioxidants shifts tropism from the lung to the liver. By contrast, the aged TME provides fewer total lipids but is rich in ceramides, leading to lower OXPHOS and high metastatic burden. Aged TME ceramides taken up by melanoma cells activate the S1P-STAT3-IL-6 signaling axis and promote liver tropism. Inhibiting OXPHOS in the young TME or blocking the IL-6 receptor in the aged TME reduces the age-specific patterns of metastasis imposed by lipid availability.

DOI: 10.1016/j.ccell.2025.04.001

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00138-2