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

Lisly Chéry, Hung Ming Lam, Ilsa Coleman, Bryce Lakely, Roger Coleman, Sandy Larson, Julio A. Aguirre-Ghiso, Jing Xia, Roman Gulati, Peter S. Nelson, Bruce Montgomery, Paul Lange, Linda A. Snyder, Robert L. Vessella, Colm Morrissey

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

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.

Original languageEnglish
Pages (from-to)9939-9951
Number of pages13
JournalOncotarget
Volume5
Issue number20
DOIs
StatePublished - 2014

Keywords

  • Dormancy
  • Gene expression
  • Metastasis
  • Prostate cancer
  • p38

Fingerprint

Dive into the research topics of 'Characterization of single disseminated prostate cancer cells reveals tumor cell heterogeneity and identifies dormancy associated pathways'. Together they form a unique fingerprint.

Cite this