Hematopoietic Age at Onset of Triple-Negative Breast Cancer Dictates Disease Aggressiveness and Progression.
Hematopoietic Age at Onset of Triple-Negative Breast Cancer Dictates Disease Aggressiveness and Progression.
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DOI：
10.1158/0008-5472.can-15-3332
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发表时间：
2016-05-15
期刊：
影响因子：
11.2
通讯作者：
McAllister SS
中科院分区：
文献类型：
--
作者：
Marsh T;Wong I;Sceneay J;Barakat A;Qin Y;Sjödin A;Alspach E;Nilsson B;Stewart SA;McAllister SS
Triple negative breast cancer (TNBC) is considered an early onset subtype of breast cancer that carries with it a poorer prognosis in young rather than older women for reasons that remain poorly understood. Hematopoiesis in the bone marrow becomes altered with age, and may therefore affect the composition of tumor-infiltrating hematopoietic cells and subsequent tumor progression. In this study, we investigated how age- and tumor-dependent changes to bone marrow-derived hematopoietic cells impact TNBC progression. Using multiple mouse models of TNBC tumorigenesis and metastasis, we found that a specific population of bone marrow cells upregulated CSF-1R and secreted the growth factor granulin (GRN) to support stromal activation and robust tumor growth in young mice. However, the same cell population in old mice expressed low levels of CSF1R and GRN, and failed to promote tumor outgrowth, suggesting that age influences the tumorigenic capacity of bone marrow cells in response to tumor-associated signals. Importantly, bone marrow cells from young mice were sufficient to activate a tumor-supportive microenvironment and induce tumor progression in old mice. These results indicate that hematopoietic age is an important determinant of TNBC aggressiveness and provide rationale for investigating age-stratified therapies designed to prevent the pro-tumorigenic effects of activated bone marrow cells.
