美国斯隆凯特琳研究所Joan Massagué课题组揭示乳腺癌脑转移起始的不同肿瘤结构和微环境。相关论文于2024年9月12日在线发表在《癌细胞》杂志上。

为了解脑转移的早期阶段，研究人员检测了两种常见的脑复发来源：三阴性乳腺癌（TNBC）和HER2阳性乳腺癌（HER2BC）。通过使用小鼠模型和人类组织样本，研究人员发现这些肿瘤类型以不同的肿瘤结构、基质界面和自分泌程序为特点在大脑中定植。

TNBC模型倾向于形成与星形胶质细胞和小胶质细胞扩散接触的血管周围鞘，而HER2BC模型则倾向于形成由自主产生的纤粘连蛋白C驱动的紧凑球体，将基质细胞隔离在外围。对肿瘤微环境的单细胞转录组学分析显示，这些结构引发了不同的阿尔茨海默病相关小胶质细胞（DAM）反应，和GAS6受体AXL的参与。这两种脑定植模式的空间特征，对利用基质治疗脑转移具有重要意义。

据介绍，脑转移是癌症的一种严重并发症，取决于播散癌细胞的初始存活、微环境适应和增殖。

附：英文原文

Title: Distinct tumor architectures and microenvironments for the initiation of breast cancer metastasis in the brain

Author: Siting Gan, Danilo G. Macalinao, Sayyed Hamed Shahoei, Lin Tian, Xin Jin, Harihar Basnet, Catherine Bibby, James T. Muller, Pranita Atri, Evan Seffar, Walid Chatila, Ali Karacay, Pharto Chanda, Anna-Katerina Hadjantonakis, Nikolaus Schultz, Edi Brogi, Tejus A. Bale, Nelson S. Moss, Rajmohan Murali, Dana Pe’er, Joan Massagué

Issue&Volume: 2024-09-12

Abstract: Brain metastasis, a serious complication of cancer, hinges on the initial survival, microenvironment adaptation, and outgrowth of disseminated cancer cells. To understand the early stages of brain colonization, we investigated two prevalent sources of cerebral relapse, triple-negative (TNBC) and HER2+ (HER2BC) breast cancers. Using mouse models and human tissue samples, we found that these tumor types colonize the brain, with a preference for distinctive tumor architectures, stromal interfaces, and autocrine programs. TNBC models tend to form perivascular sheaths with diffusive contact with astrocytes and microglia. In contrast, HER2BC models tend to form compact spheroids driven by autonomous tenascin C production, segregating stromal cells to the periphery. Single-cell transcriptomics of the tumor microenvironment revealed that these architectures evoke differential Alzheimer’s disease-associated microglia (DAM) responses and engagement of the GAS6 receptor AXL. The spatial features of the two modes of brain colonization have relevance for leveraging the stroma to treat brain metastasis.

DOI: 10.1016/j.ccell.2024.08.015

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(24)00314-3