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Accepted (AM)Open Access (License Unspecified), Open
Journal article
COOPERATION AMONG HETEROGENEOUS PROSTATE CANCER CELLS IN THE BONE METASTATIC NICHE
Oncogene, v 36(20), pp 2846-2856
19 Dec 2016
PMCID: PMC5436952
PMID: 27991924
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The growth of disseminated tumor cells (DTCs) into metastatic lesions depends on the establishment of a favorable microenvironment in the stroma of the target organs. Here we show that mice treated with anakinra, an antagonist of the IL-1β receptor (IL-1R), or harboring a targeted deletion of IL-1R are significantly less prone to develop bone tumors when inoculated in the arterial circulation with human prostate cancer (PCa) cells expressing IL-1β. Interestingly, human mesenchymal stem cells (hMSCs) exposed
in vitro
to medium conditioned by IL-1β-expressing cancer cells responded by up regulating S100A4, a marker of cancer-associated fibroblasts (CAFs), and this effect was blocked by anakinra. Analogously, the stroma adjacent to skeletal metastases generated in mice by IL-1β-expressing cancer cells showed a dramatic increase in S100A4, COX-2 and the alteration of thirty tumor-related genes as measured by Nanostring analysis. These effects were not observed in the stroma associated to the rare and much smaller metastases generated by the same cells in IL-1R knockout animals, confirming that tumor-secreted IL-1β generates skeletal CAFs and conditions the surrounding bone microenvironment. In skeletal lesions from patients with metastatic PCa, histological and molecular analyses revealed that IL-1β is highly expressed in cancer cells in which the androgen receptor (AR) is not detected (AR−) whereas this cytokine is uniformly absent in the AR-positive (AR+) metastatic cells. The stroma conditioned by IL-1β-expressing cancer cells served as a supportive niche also for coexisting IL-1β-lacking cancer cells, which are otherwise unable to generate tumors after independently seeding the skeleton of mice. This niche is established very early following tumor seeding and hints to a role of IL-1β in promoting early colonization of PCa at the skeletal level.
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Details
- Title
- COOPERATION AMONG HETEROGENEOUS PROSTATE CANCER CELLS IN THE BONE METASTATIC NICHE
- Creators
- Kristina Shahriari - Drexel UniversityFei Shen - Drexel UniversityAsurayya Worrede-Mahdi - Drexel UniversityQingxin Liu - Drexel UniversityYulan Gong - Drexel UniversityFernando U. Garcia - Drexel UniversityAlessandro Fatatis - Drexel University
- Publication Details
- Oncogene, v 36(20), pp 2846-2856
- Publisher
- Springer Nature
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology; Pathology (and Laboratory Medicine)
- Web of Science ID
- WOS:000401697800007
- Scopus ID
- 2-s2.0-85006416089
- Other Identifier
- 991019168181204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Genetics & Heredity
- Oncology