Combined Genome and Transcriptome Analysis of Single Disseminated Cancer Cells from Bone Marrow of Prostate Cancer Patients Reveals Unexpected Transcriptomes

Guzvic, Miodrag and Braun, Bernhard and Ganzer, Roman and Burger, Maximilian and Nerlich, Michael and Winkler, Sebastian and Werner-Klein, Melanie and Czyz, Zbigniew T. and Polzer, Bernhard and Klein, Christoph A. (2014) Combined Genome and Transcriptome Analysis of Single Disseminated Cancer Cells from Bone Marrow of Prostate Cancer Patients Reveals Unexpected Transcriptomes. CANCER RESEARCH, 74 (24). pp. 7383-7394. ISSN 0008-5472, 1538-7445

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Abstract

Bone is the most frequent site of metastasis in prostate cancer and patients with bone metastases are deemed incurable. Targeting prostate cancer cells that disseminated to the bone marrow before surgery and before metastatic outgrowth may therefore prevent lethal metastasis. This prompted us to directly analyze the transcriptome of disseminated cancer cells (DCC) isolated from patients with nonmetastatic (UICC stage M0) prostate cancer. We screened 105 bone marrow samples of patients with M0-stage prostate cancer and 18 bone marrow 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, whereas true DCCs may express hematopoietic transcripts. These results point to an unexpected transcriptome plasticity of epithelial cancer cells in bone marrow and question common transcriptional criteria to identify DCCs. (C) 2014 AACR.

Item Type: Article
Uncontrolled Keywords: DISSEMINATED TUMOR-CELLS; BREAST-CANCER; ADHESION MOLECULE; ERYTHROID-CELLS; PERIPHERAL-BLOOD; EPITHELIAL-CELLS; POSITIVE CELLS; ANTIBODY 9C4; STEM-CELLS; IN-VITRO;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Unfallchirurgie
Medicine > Lehrstuhl für Immunologie
Medicine > Lehrstuhl für Orthopädie
Medicine > Lehrstuhl für Urologie
Medicine > Lehrstuhl für experimentelle Medizin und Therapieverfahren
Depositing User: Dr. Gernot Deinzer
Date Deposited: 05 Aug 2019 13:23
Last Modified: 05 Aug 2019 13:23
URI: https://pred.uni-regensburg.de/id/eprint/9047

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