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

Marsh, Timothy; Wong, Irene; Sceneay, Jaclyn; Barakat, Amey; Qin, Yuanbo; Sjodin, Andreas; Alspach, Elise; Nilsson, Björn LU ; Stewart, Sheila A. and Mcallister, Sandra S. (2016) In Cancer Research 76(10). p.2932-2943
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... (More)

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.

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author
organization
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type
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publication status
published
subject
in
Cancer Research
volume
76
issue
10
pages
12 pages
publisher
American Association for Cancer Research
external identifiers
  • Scopus:84971528846
  • WOS:000375841000012
ISSN
0008-5472
DOI
10.1158/0008-5472.CAN-15-3332
language
English
LU publication?
yes
id
8240d0d0-e827-4918-9a23-7a27757bfef4
date added to LUP
2016-06-28 16:21:59
date last changed
2017-01-01 08:29:17
@article{8240d0d0-e827-4918-9a23-7a27757bfef4,
  abstract     = {<p>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.</p>},
  author       = {Marsh, Timothy and Wong, Irene and Sceneay, Jaclyn and Barakat, Amey and Qin, Yuanbo and Sjodin, Andreas and Alspach, Elise and Nilsson, Björn and Stewart, Sheila A. and Mcallister, Sandra S.},
  issn         = {0008-5472},
  language     = {eng},
  month        = {05},
  number       = {10},
  pages        = {2932--2943},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer Research},
  title        = {Hematopoietic age at onset of triple-negative breast cancer dictates disease aggressiveness and progression},
  url          = {http://dx.doi.org/10.1158/0008-5472.CAN-15-3332},
  volume       = {76},
  year         = {2016},
}