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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Standard

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; Stewart, Sheila A.; Mcallister, Sandra S.

I: Cancer Research, Vol. 76, Nr. 10, 15.05.2016, s. 2932-2943.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Marsh, T, Wong, I, Sceneay, J, Barakat, A, Qin, Y, Sjodin, A, Alspach, E, Nilsson, B, Stewart, SA & Mcallister, SS 2016, 'Hematopoietic age at onset of triple-negative breast cancer dictates disease aggressiveness and progression', Cancer Research, vol. 76, nr. 10, s. 2932-2943. https://doi.org/10.1158/0008-5472.CAN-15-3332

APA

Marsh, T., Wong, I., Sceneay, J., Barakat, A., Qin, Y., Sjodin, A., ... Mcallister, S. S. (2016). Hematopoietic age at onset of triple-negative breast cancer dictates disease aggressiveness and progression. Cancer Research, 76(10), 2932-2943. https://doi.org/10.1158/0008-5472.CAN-15-3332

CBE

Marsh T, Wong I, Sceneay J, Barakat A, Qin Y, Sjodin A, Alspach E, Nilsson B, Stewart SA, Mcallister SS. 2016. Hematopoietic age at onset of triple-negative breast cancer dictates disease aggressiveness and progression. Cancer Research. 76(10):2932-2943. https://doi.org/10.1158/0008-5472.CAN-15-3332

MLA

Vancouver

Author

Marsh, Timothy ; Wong, Irene ; Sceneay, Jaclyn ; Barakat, Amey ; Qin, Yuanbo ; Sjodin, Andreas ; Alspach, Elise ; Nilsson, Björn ; Stewart, Sheila A. ; Mcallister, Sandra S. / Hematopoietic age at onset of triple-negative breast cancer dictates disease aggressiveness and progression. I: Cancer Research. 2016 ; Vol. 76, Nr. 10. s. 2932-2943.

RIS

TY - JOUR

T1 - Hematopoietic age at onset of triple-negative breast cancer dictates disease aggressiveness and progression

AU - Marsh, Timothy

AU - Wong, Irene

AU - Sceneay, Jaclyn

AU - Barakat, Amey

AU - Qin, Yuanbo

AU - Sjodin, Andreas

AU - Alspach, Elise

AU - Nilsson, Björn

AU - Stewart, Sheila A.

AU - Mcallister, Sandra S.

PY - 2016/5/15

Y1 - 2016/5/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84971528846&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-15-3332

DO - 10.1158/0008-5472.CAN-15-3332

M3 - Article

VL - 76

SP - 2932

EP - 2943

JO - Cancer research. Supplement

T2 - Cancer research. Supplement

JF - Cancer research. Supplement

SN - 1538-7445

IS - 10

ER -