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Published, Version of Record (VoR)CC BY V4.0, Open
Journal article
Stromal cyclin D1 promotes heterotypic immune signaling and breast cancer growth
Oncotarget, v 8(47), pp 81754-81775
04 Aug 2017
PMCID: PMC5669846
PMID: 29137220
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The
cyclin D1
gene encodes the regulatory subunit of a holoenzyme that drives cell autonomous cell cycle progression and proliferation. Herein we show cyclin D1 abundance is increased >30-fold in the stromal fibroblasts of patients with invasive breast cancer, associated with poor outcome. Cyclin D1 transformed hTERT human fibroblast to a cancer-associated fibroblast phenotype. Stromal fibroblast expression of cyclin D1 (cyclin D1
Stroma
)
in vivo
, enhanced breast epithelial cancer tumor growth, restrained apoptosis, and increased autophagy. Cyclin D1
Stroma
had profound effects on the breast tumor microenvironment increasing the recruitment of F4/80
+
and CD11b
+
macrophages and increasing angiogenesis. Cyclin D1
Stroma
induced secretion of factors that promoted expansion of stem cells (breast stem-like cells, embryonic stem cells and bone marrow derived stem cells). Cyclin D1
Stroma
resulted in increased secretion of proinflammatory cytokines (CCL2, CCL7, CCL11, CXCL1, CXCL5, CXCL9, CXCL12), CSF (CSF1, GM-CSF1) and osteopontin (OPN) (30-fold). OPN was induced by cyclin D1 in fibroblasts, breast epithelial cells and in the murine transgenic mammary gland and OPN was sufficient to induce stem cell expansion. These results demonstrate that cyclin D1
Stroma
drives tumor microenvironment heterocellular signaling, promoting several key hallmarks of cancer.
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Details
- Title
- Stromal cyclin D1 promotes heterotypic immune signaling and breast cancer growth
- Creators
- Timothy G. Pestell - Thomas Jefferson UniversityXuanmao Jiao - Baruch S. Blumberg InstituteMukesh Kumar - Thomas Jefferson UniversityAmy R. Peck - Medical College of WisconsinMarco Prisco - Thomas Jefferson UniversityShengqiong Deng - Thomas Jefferson UniversityZhiping Li - Thomas Jefferson UniversityAdam Ertel - Thomas Jefferson UniversityMathew C. Casimiro - Pennsylvania Cancer and Regenerative Medicine Research Center, Baruch S. Blumberg Institute, Pennsylvania Biotechnology Center, Wynnewood, PA, USAXiaoming Ju - Thomas Jefferson UniversityAgnese Di Rocco - Baruch S. Blumberg InstituteGabriele Di Sante - Baruch S. Blumberg InstituteSanjay Katiyar - Thomas Jefferson UniversityAlison Shupp - Thomas Jefferson UniversityMichael P. Lisanti - University of SalfordPooja Jain - Drexel UniversityKongming Wu - Tongji Medical CollegeHallgeir Rui - Medical College of WisconsinDouglas C. Hooper - Thomas Jefferson UniversityZuoren Yu - Tongji UniversityAaron R. Goldman - The Wistar InstituteDavid W. Speicher - The Wistar InstituteLisa Laury-Kleintop - Lankenau Institute for Medical ResearchRichard G. Pestell - Nanyang Technological University
- Publication Details
- Oncotarget, v 8(47), pp 81754-81775
- Publisher
- Impact Journals LLC
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology; School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000412683900012
- Scopus ID
- 2-s2.0-85030853948
- Other Identifier
- 991019168343704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell Biology
- Oncology