Lung-resident alveolar macrophages regulate the timing of breast cancer metastasis

IF 45.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Cell Pub Date : 2024-10-07 DOI:10.1016/j.cell.2024.09.016

Erica Dalla, Michael Papanicolaou, Matthew D. Park, Nicole Barth, Rui Hou, Deisy Segura-Villalobos, Luis Valencia Salazar, Dan Sun, Alistair R.R. Forrest, Maria Casanova-Acebes, David Entenberg, Miriam Merad, Julio A. Aguirre-Ghiso

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Abstract

Breast disseminated cancer cells (DCCs) can remain dormant in the lungs for extended periods, but the mechanisms limiting their expansion are not well understood. Research indicates that tissue-resident alveolar macrophages suppress breast cancer metastasis in lung alveoli by inducing dormancy. Through ligand-receptor mapping and intravital imaging, it was found that alveolar macrophages express transforming growth factor (TGF)-β2. This expression, along with persistent macrophage-cancer cell interactions via the TGF-βRIII receptor, maintains cancer cells in a dormant state. Depleting alveolar macrophages or losing the TGF-β2 receptor in cancer cells triggers metastatic awakening. Aggressive breast cancer cells are either suppressed by alveolar macrophages or evade this suppression by avoiding interaction and downregulating the TGF-β2 receptor. Restoring TGF-βRIII in aggressive cells reinstates TGF-β2-mediated macrophage growth suppression. Thus, alveolar macrophages act as a metastasis immune barrier, and downregulation of TGF-β2 signaling allows cancer cells to overcome macrophage-mediated growth suppression.

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肺驻留肺泡巨噬细胞调控乳腺癌转移的时机

乳腺播散性癌细胞（DCC）可在肺部长期休眠，但限制其扩展的机制尚不十分清楚。研究表明，组织驻留的肺泡巨噬细胞通过诱导休眠来抑制乳腺癌在肺泡中的转移。通过配体受体映射和眼内成像，研究发现肺泡巨噬细胞表达转化生长因子（TGF）-β2。这种表达以及巨噬细胞与癌细胞通过 TGF-βRIII 受体持续发生的相互作用，使癌细胞处于休眠状态。消耗肺泡巨噬细胞或失去癌细胞中的 TGF-β2 受体会引发转移性觉醒。侵袭性乳腺癌细胞要么受到肺泡巨噬细胞的抑制，要么通过避免相互作用和下调 TGF-β2 受体来逃避这种抑制。恢复侵袭性细胞中的 TGF-βRIII 可恢复 TGF-β2 介导的巨噬细胞生长抑制。因此，肺泡巨噬细胞是转移的免疫屏障，下调 TGF-β2 信号可使癌细胞克服巨噬细胞介导的生长抑制。

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来源期刊

Cell 生物-生化与分子生物学

CiteScore

110.00

自引率

0.80%

发文量

396

审稿时长

2 months

期刊介绍： Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO). The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries. In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.

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