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Oncotarget. 2014 Oct 30;5(20):9939-51.

Characterization of single disseminated prostate cancer cells reveals tumor cell heterogeneity and identifies dormancy associated pathways.

Author information

1
Department of Urology, University of Washington, Seattle, WA. Contributed equally to this work.
2
Divison of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA.
3
Department of Urology, University of Washington, Seattle, WA.
4
Division of Hematology and Oncology, Department of Medicine and Department of Otolaryngology, Tisch Cancer Institute, Black Family Stem Cell Institute, Ichan School of Medicine at Mount Sinai, New York, NY.
5
Divison of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
6
Divison of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA. Department of Medicine, University of Washington, Seattle, WA.
7
Department of Medicine, University of Washington, Seattle, WA.
8
Department of Veterans Affairs Medical Center, Seattle, WA. Department of Urology, University of Washington, Seattle, WA.
9
Janssen Research and Development, LLC, Spring House, PA.

Abstract

Cancer dormancy refers to the prolonged clinical disease-free time between removal of the primary tumor and recurrence, which is common in prostate cancer (PCa), breast cancer, esophageal cancer, and other cancers. PCa disseminated tumor cells (DTC) are detected in both patients with no evidence of disease (NED) and advanced disease (ADV). However, the molecular and cellular nature of DTC is unknown. We performed a first-in-field study of single DTC transcriptomic analyses in cancer patients to identify a molecular signature associated with cancer dormancy. We profiled eighty-five individual EpCAM⁺/CD45⁻ cells from the bone marrow of PCa patients with NED or ADV. We analyzed 44 DTC with high prostate-epithelial signatures, and eliminated 41 cells with high erythroid signatures and low prostate epithelial signatures. DTC were clustered into 3 groups: NED, ADV_1, and ADV_2, in which the ADV_1 group presented a distinct gene expression pattern associated with the p38 stress activated kinase pathway. Additionally, DTC from the NED group were enriched for a tumor dormancy signature associated with head and neck squamous carcinoma and breast cancer. This study provides the first clinical evidence of the p38 pathway as a potential biomarker for early recurrence and an attractive target for therapeutic intervention.

PMID:
25301725
PMCID:
PMC4259449
DOI:
10.18632/oncotarget.2480
[Indexed for MEDLINE]
Free PMC Article

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