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Hematopoietic age at onset of triple-negative breast cancer dictates disease aggressiveness and progression

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Author

  • Timothy Marsh
  • Irene Wong
  • Jaclyn Sceneay
  • Amey Barakat
  • Yuanbo Qin
  • Andreas Sjodin
  • Elise Alspach
  • Björn Nilsson
  • Sheila A. Stewart
  • Sandra S. Mcallister

Summary, in English

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 (BMC) upregulated CSF-1R and secreted the growth factor granulin 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 granulin and failed to promote tumor outgrowth, suggesting that age influences the tumorigenic capacity of BMCs in response to tumor-associated signals. Importantly, BMCs 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 protumorigenic effects of activated BMCs.

Department/s

Publishing year

2016-05-15

Language

English

Pages

2932-2943

Publication/Series

Cancer Research

Volume

76

Issue

10

Document type

Journal article

Publisher

American Association for Cancer Research Inc.

Topic

  • Cell and Molecular Biology
  • Cancer and Oncology

Status

Published

ISBN/ISSN/Other

  • ISSN: 0008-5472