Bone marrow–derived fibroblasts are a functionally distinct stromal cell population in breast cancer
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- Yael Raz
- Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel 1
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- Noam Cohen
- Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel 1
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- Ophir Shani
- Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel 1
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- Rachel E. Bell
- Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel 3
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- Sergey V. Novitskiy
- Department of Cancer Biology, Vanderbilt University School of Medicine and Vanderbilt-Ingram Comprehensive Cancer Center, Nashville, TN 4
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- Lilach Abramovitz
- Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel 1
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- Carmit Levy
- Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel 3
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- Michael Milyavsky
- Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel 1
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- Leonor Leider-Trejo
- Department of Pathology, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel 5
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- Harold L. Moses
- Department of Cancer Biology, Vanderbilt University School of Medicine and Vanderbilt-Ingram Comprehensive Cancer Center, Nashville, TN 4
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- Dan Grisaru
- Department of Obstetrics and Gynecology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel 2
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- Neta Erez
- Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel 1
説明
<jats:p>Cancer-associated fibroblasts (CAFs) are highly prominent in breast tumors, but their functional heterogeneity and origin are still largely unresolved. We report that bone marrow (BM)–derived mesenchymal stromal cells (MSCs) are recruited to primary breast tumors and to lung metastases and differentiate to a distinct subpopulation of CAFs. We show that BM-derived CAFs are functionally important for tumor growth and enhance angiogenesis via up-regulation of Clusterin. Using newly generated transgenic mice and adoptive BM transplantations, we demonstrate that BM-derived fibroblasts are a substantial source of CAFs in the tumor microenvironment. Unlike resident CAFs, BM-derived CAFs do not express PDGFRα, and their recruitment resulted in a decrease in the percentage of PDGFRα-expressing CAFs. Strikingly, decrease in PDGFRα in breast cancer patients was associated with worse prognosis, suggesting that BM-derived CAFs may have deleterious effects on survival. Therefore, PDGFRα expression distinguishes two functionally unique CAF populations in breast tumors and metastases and may have important implications for patient stratification and precision therapeutics.</jats:p>
収録刊行物
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- Journal of Experimental Medicine
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Journal of Experimental Medicine 215 (12), 3075-3093, 2018-11-23
Rockefeller University Press