Bone is the most frequent site of metastasis in prostate cancer (PCa) and patients with bone metastases are deemed incurable.
Targeting prostate cancer cells that disseminated to the bone marrow (BM) prior to surgery and before metastatic outgrowth may therefore prevent lethal metastasis. This prompted us to directly analyse the transcriptome of disseminated cancer cells (DCC) isolated from non-metastatic (UICC stage M0) prostate cancer patients. We screened 105 BM samples of M0-stage prostate cancer patients and 18 BM samples of patients without malignancy for the presence of EpCAM+ single cells. In total we isolated 270 cells from both groups by micromanipulation and globally amplified their mRNA. We used targeted transcriptional profiling to unambiguously identify DCCs for subsequent in-depth analysis. Transcriptomes of all cells were examined for the expression of EPCAM, KRT8, KRT18, KRT19, KRT14, KRT6a, KRT5, KLK3 (PSA), MAGEA2, MAGEA4, PTPRC (CD45), CD33, CD34, CD19, GYPC, SCL4A1 (band 3), and HBA2. Using these transcripts we found it impossible to reliably identify true DCCs. We then applied combined genome and transcriptome analysis of single cells and found that EpCAM+ cells from controls expressed transcripts thought to be epithelial-specific, while true DCCs may express haematopoietic transcripts. These results point to an unexpected transcriptome plasticity of epithelial cancer cells in bone marrow and question common transcriptional criteria to identify DCCs.
Written by:
Guzvic M, Braun B, Ganzer R, Burger M, Nerlich M, Winkler S, Werner-Klein M, Czyz ZT, Polzer B, Klein CA. Are you the author?
Chair of Experimental Medicine and Therapy Research, University of Regensburg; Department of Urology, Caritas-Hospital St. Josef; Department of Trauma Surgery, University Hospital Regensburg; Department of Orthopaedic Surgery, University of Regensburg; Department of Immunology, University of Regensburg; Project Group Personalized Tumour Therapy, Fraunhofer Institute of Experimental Medicine and Toxicology; Chair of Experimental Medicine and Therapy Research, University of Regensburg.
Reference: Cancer Res. 2014 Oct 15. pii: canres.0934.2014.
doi: 10.1158/0008-5472.CAN-14-0934
PubMed Abstract
PMID: 25320011