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肺驻留肺泡巨噬细胞调节乳腺癌转移的时机。

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

机构信息

Division of Hematology and Oncology, Department of Medicine and Department of Otolaryngology, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Cancer Dormancy Institute, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Ruth L. and David S. Gottesman Institute for Stem Cell Research and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA.

出版信息

Cell. 2024 Nov 14;187(23):6631-6648.e20. doi: 10.1016/j.cell.2024.09.016. Epub 2024 Oct 7.

DOI:10.1016/j.cell.2024.09.016
PMID:39378878
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11568918/
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.

摘要

乳腺播散癌细胞（DCC）在肺部可能会休眠很长时间，但限制其扩散的机制尚不清楚。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肺泡中的转移。通过配体-受体映射和活体成像，发现肺泡巨噬细胞表达转化生长因子（TGF）-β2。这种表达，以及通过 TGF-βRIII 受体持续的巨噬细胞-癌细胞相互作用，使癌细胞处于休眠状态。耗尽肺泡巨噬细胞或在癌细胞中丢失 TGF-β2 受体会触发转移觉醒。侵袭性乳腺癌细胞要么被肺泡巨噬细胞抑制，要么通过避免相互作用和下调 TGF-β2 受体来逃避这种抑制。在侵袭性细胞中恢复 TGF-βRIII 会重新建立 TGF-β2 介导的巨噬细胞生长抑制。因此，肺泡巨噬细胞作为转移免疫屏障，TGF-β2 信号通路的下调允许癌细胞克服巨噬细胞介导的生长抑制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc01/11568918/3a3aa907587b/nihms-2024329-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc01/11568918/d557e1437554/nihms-2024329-f0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc01/11568918/6d917eda792f/nihms-2024329-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc01/11568918/f11671fb733d/nihms-2024329-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc01/11568918/75ce4bfd4f9d/nihms-2024329-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc01/11568918/3a977769fd7f/nihms-2024329-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc01/11568918/3a3aa907587b/nihms-2024329-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc01/11568918/d557e1437554/nihms-2024329-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc01/11568918/8ad0d883fd4d/nihms-2024329-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc01/11568918/6d917eda792f/nihms-2024329-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc01/11568918/f11671fb733d/nihms-2024329-f0004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc01/11568918/3a977769fd7f/nihms-2024329-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc01/11568918/3a3aa907587b/nihms-2024329-f0007.jpg

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