Distinct tumor architectures and microenvironments for the initiation of breast cancer metastasis in the brain Journal Article
| Authors: | Gan, S.; Macalinao, D. G.; Shahoei, S. H.; Tian, L.; Jin, X.; Basnet, H.; Bibby, C.; Muller, J. T.; Atri, P.; Seffar, E.; Chatila, W.; Karacay, A.; Chanda, P.; Hadjantonakis, A. K.; Schultz, N.; Brogi, E.; Bale, T. A.; Moss, N. S.; Murali, R.; Pe'er, D.; Massagué, J. |
| Article Title: | Distinct tumor architectures and microenvironments for the initiation of breast cancer metastasis in the brain |
| 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. Copyright © 2024 Elsevier Inc. All rights reserved. |
| Keywords: | genetics; brain tumor; brain neoplasms; mouse; animal; metabolism; animals; mice; breast cancer; epidermal growth factor receptor 2; astrocyte; pathology; cell line, tumor; protein tyrosine kinase; breast neoplasms; extracellular matrix; breast tumor; tumor cell line; brain metastasis; receptor, erbb-2; receptor protein-tyrosine kinases; stroma cell; stromal cells; axl receptor tyrosine kinase; astrocytes; tumor microenvironment; erbb2 protein, human; triple negative breast cancer; microglia; tenascin; tumor architecture; humans; human; female; triple negative breast neoplasms |
| Journal Title: | Cancer Cell |
| Volume: | 42 |
| Issue: | 10 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2024-10-14 |
| Start Page: | 1693 |
| End Page: | 1712 |
| Language: | English |
| DOI: | 10.1016/j.ccell.2024.08.015 |
| PUBMED: | 39270646 |
| PROVIDER: | scopus |
| PMCID: | PMC12093277 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is Joan Massague -- Source: Scopus |
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