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

Gužvić, Miodrag; Braun, Bernhard; Ganzer, Roman; Burger, Maximilian; Nerlich, Michael; Winkler, Sebastian; Werner-Klein, Melanie; Czyż, Zbigniew T.; Polzer, Bernhard; Klein, Christoph

doi:10.1158/0008-5472.can-14-0934

Cited by 44 publications

(38 citation statements)

References 43 publications

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“…The human bone marrow can become populated with tumor cells of breast cancer patients [60], as well as prostate cancer [61]. It has been demonstrated that disseminated tumor cells inhabiting bone marrow stroma can lead to reduction of hematopoiesis and level of SDF-1.…”

Section: Mscs: Recruitment and Functions In Tmementioning

confidence: 99%

“…It has been demonstrated that disseminated tumor cells inhabiting bone marrow stroma can lead to reduction of hematopoiesis and level of SDF-1. Moreover, it has been found that disseminated tumor cells express markers of hematopoietic cells presented in bone marrow, thus mimicking microenvironmental marker pattern expression, which complicate detection of tumor cells and may contribute to inefficiency of therapeutics [61]. Also, CXCR4/SDF-1 signaling has been shown to be involved in the homing and proliferation of leukemia cells in acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and other hematologic malignancies.…”

Section: Mscs: Recruitment and Functions In Tmementioning

confidence: 99%

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The Roles of Mesenchymal Stromal/Stem Cells in Tumor Microenvironment Associated with Inflammation

Trivanović

Krstić

Djordjević

et al. 2016

Mediators of Inflammation

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State of tumor microenvironment (TME) is closely linked to regulation of tumor growth and progression affecting the final outcome, refractoriness, and relapse of disease. Interactions of tumor, immune, and mesenchymal stromal/stem cells (MSCs) have been recognized as crucial for understanding tumorigenesis. Due to their outstanding features, stem cell-like properties, capacity to regulate immune response, and dynamic functional phenotype dependent on microenvironmental stimuli, MSCs have been perceived as important players in TME. Signals provided by tumor-associated chronic inflammation educate MSCs to alter their phenotype and immunomodulatory potential in favor of tumor-biased state of MSCs. Adjustment of phenotype to TME and acquisition of tumor-promoting ability by MSCs help tumor cells in maintenance of permissive TME and suppression of antitumor immune response. Potential utilization of MSCs in treatment of tumor is based on their inherent ability to home tumor tissue that makes them suitable delivery vehicles for immune-stimulating factors and vectors for targeted antitumor therapy. Here, we review data regarding intrusive effects of inflammatory TME on MSCs capacity to affect tumor development through modification of their phenotype and interactions with immune system.

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Section: Mscs: Recruitment and Functions In Tmementioning

confidence: 99%

Section: Mscs: Recruitment and Functions In Tmementioning

confidence: 99%

The Roles of Mesenchymal Stromal/Stem Cells in Tumor Microenvironment Associated with Inflammation

Trivanović

Krstić

Djordjević

et al. 2016

Mediators of Inflammation

View full text Add to dashboard Cite

show abstract

“…Our subsequent study on a single cell transcriptomic analysis demonstrated that a significant portion of the EpCAM-positive cells expressed a signature associated with erythroid progenitor-like cells [6,23,24]. An independent single cell gene expression study by Gužvić et al reported an interesting population of cells that expressed prostate epithelial markers, genomically aberrant, EpCAM-positive but CK8- and CK18-negative, suggesting a potential loss of CK epithelial markers in these DTC [15]. Therefore, while anti-EpCAM antibody may capture some non-epithelial cells (e.g.…”

Section: Detection Of Dtcmentioning

confidence: 99%

“…To understand the biology behind the DTC and its relation to tumor dormancy, we [6,30] and others [15] recently profiled single DTC in the bone marrow of PCa patients at different stages of disease progression. DTC displayed high intra- and inter-patient heterogeneity [6,15].…”

Section: The Transcriptomic Profile Of Dtc Is Heterogeneous In Patientsmentioning

confidence: 99%

“…DTC displayed high intra- and inter-patient heterogeneity [6,15]. Gužvić et al, using a single cell genomic and gene expression analysis, reported that the genomically aberrant DTC isolated from PCa patients regardless of the metastatic status were highly plastic [15]. Furthermore, a global gene expression analysis on DTC isolated from PCa NED patients 7–18 years post-RP was compared with those from patients with advanced disease (i.e.…”

Section: The Transcriptomic Profile Of Dtc Is Heterogeneous In Patientsmentioning

confidence: 99%

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The biology and clinical implications of prostate cancer dormancy and metastasis

et al. 2015

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Disseminated tumor cells (DTC) are detected early in the disease process in prostate cancer (PCa) patients and can persist after radical prostatectomy. DTC can remain dormant in patients with no evidence of disease for a prolonged period of time only to recur 10 or more years later. Recent advances in single cell genomics and transcriptomics have provided much needed insight into DTC biology and cancer dormancy in patients. With the development of new in vitro and preclinical models, researchers recapitulate the clinical events in patients and therefore allow further elucidation of the molecular mechanisms underlying cancer dormancy and escape. In this review we explore novel ideas on the detection, heterogeneous transcriptomic profiles, molecular and cellular mechanisms of dormancy, and potential mechanisms underlying dormancy escape by DTC. As such there is hope that identifying and targeting novel dormancy-associated pathways in patients with residual disease will have significant clinical implications for the treatment of PCa patients in the future.

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Circulating and disseminated tumor cells: harbingers or initiators of metastasis?

2017

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Tumor cells leave the primary tumor and enter the circulation. Once there, they are called circulating tumor cells (CTCs). A fraction of CTCs are capable of entering distant sites and persisting as disseminated tumor cells (DTCs). An even smaller fraction of DTCs are capable of progressing toward metastases. It is known that the DTC microenvironment plays an important role in sustaining their survival, regulating their growth, and conferring resistance to therapy. But we still have much to learn about the nature of these rare cell populations to predict which will progress and what exactly should cause concern for future relapse. Although recent technological advances in our ability to detect and molecularly and functionally characterize CTCs and DTCs promise to unravel this ambiguity, the timing of dissemination and the precise source of CTCs and DTCs profiled will impact the conclusions that can be made from these endeavors. In this review, we discuss the biology of CTCs and DTCs; the technologies to detect, isolate, and profile these cells; and the exceptions we must apply to our understanding of what role these cells play in the metastatic process. We conclude that a greater effort to understand the unique biology of these cells in context will positively impact our ability to use these cells to predict outcome, monitor treatment efficacy, and reveal therapeutically relevant targets to deplete these populations and ultimately prevent metastasis.

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

Cited by 44 publications

References 43 publications

The Roles of Mesenchymal Stromal/Stem Cells in Tumor Microenvironment Associated with Inflammation

The Roles of Mesenchymal Stromal/Stem Cells in Tumor Microenvironment Associated with Inflammation

The biology and clinical implications of prostate cancer dormancy and metastasis

Circulating and disseminated tumor cells: harbingers or initiators of metastasis?

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