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Updated: Apr 22, 2026
Isolation of Cancer Stem Cells From Human Prostate Cancer Samples
Published on: March 14, 2014
Combined genome and transcriptome analysis of single disseminated cancer cells from bone marrow of prostate cancer
Miodrag Gužvić1, Bernhard Braun2, Roman Ganzer3
1Chair of Experimental Medicine and Therapy Research, University of Regensburg, Regensburg, Germany.
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.
Insights
Identifying disseminated prostate cancer cells (DCCs) in bone marrow is challenging. These cells exhibit unexpected plasticity, expressing hematopoietic transcripts instead of typical epithelial markers, questioning current identification methods.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metastasis Research
Background:
- Bone is the most common site for prostate cancer metastasis, and patients with bone metastases are considered incurable.
- Early detection and targeting of disseminated cancer cells (DCCs) in bone marrow before metastasis outgrowth could potentially prevent lethal disease progression.
Purpose of the Study:
- To directly analyze the transcriptome of DCCs isolated from patients with nonmetastatic (UICC stage M0) prostate cancer.
- To evaluate the reliability of common transcriptional markers for identifying DCCs in bone marrow.
Main Methods:
- Screened 105 bone marrow samples from M0 prostate cancer patients and 18 from non-malignant controls for EpCAM(+) single cells.
- Isolated 270 cells via micromanipulation and performed global mRNA amplification.
- Utilized targeted transcriptional profiling and combined genome/transcriptome analysis for cell identification.
Main Results:
- Initial targeted profiling using epithelial markers (e.g., EPCAM, KRTs) and prostate cancer markers (e.g., KLK3) failed to reliably identify true DCCs.
- EpCAM(+) cells from controls expressed epithelial transcripts, while identified DCCs unexpectedly expressed hematopoietic transcripts.
- Demonstrated significant transcriptome plasticity in epithelial cancer cells residing in the bone marrow.
Conclusions:
- Commonly used transcriptional criteria for identifying DCCs in bone marrow are unreliable due to unexpected cellular plasticity.
- Further research is needed to develop accurate methods for detecting and characterizing disseminated prostate cancer cells in the bone marrow.
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