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

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • Timothy Marsh
  • Irene Wong
  • Jaclyn Sceneay
  • Amey Barakat
  • Yuanbo Qin
  • Andreas Sjodin
  • Elise Alspach
  • Björn Nilsson
  • Sheila A. Stewart
  • Sandra S. Mcallister
Organisations
External organisations
  • Brigham and Women's Hospital / Harvard Medical School
  • Harvard University
  • Washington University in St. Louis
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
  • Cancer and Oncology
Original languageEnglish
Pages (from-to)2932-2943
Number of pages12
JournalCancer Research
Volume76
Issue number10
Publication statusPublished - 2016 May 15
Publication categoryResearch
Peer-reviewedYes