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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.
- Source :
-
Cancer research [Cancer Res] 2016 May 15; Vol. 76 (10), pp. 2932-43. Date of Electronic Publication: 2016 Apr 07. - Publication Year :
- 2016
-
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. Cancer Res; 76(10); 2932-43. ©2016 AACR.<br /> (©2016 American Association for Cancer Research.)
- Subjects :
- Age Factors
Age of Onset
Animals
Apoptosis
Blotting, Western
Bone Marrow Cells metabolism
Cell Proliferation
Disease Progression
Female
Flow Cytometry
Humans
Intercellular Signaling Peptides and Proteins genetics
Intercellular Signaling Peptides and Proteins metabolism
Mice
Mice, Nude
Progranulins
RNA, Messenger genetics
Real-Time Polymerase Chain Reaction
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor genetics
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor metabolism
Reverse Transcriptase Polymerase Chain Reaction
Triple Negative Breast Neoplasms genetics
Triple Negative Breast Neoplasms metabolism
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Bone Marrow Cells pathology
Hematopoiesis physiology
Triple Negative Breast Neoplasms pathology
Tumor Microenvironment
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7445
- Volume :
- 76
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 27197230
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-15-3332