Oncotarget

Priority Research Papers:

Mesenchymal stem cell infiltration during neoplastic transformation of the human prostate

W. Nathaniel Brennen _, Baohui Zhang, Ibrahim Kulac, L. Nelleke Kisteman, Lizamma Antony, Hao Wang, Alan K. Meeker, Angelo M. De Marzo, Isla P. Garraway, Samuel R. Denmeade and John T. Isaacs

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Oncotarget. 2017; 8:46710-46727. https://doi.org/10.18632/oncotarget.17362

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Abstract

W. Nathaniel Brennen1, Baohui Zhang2, Ibrahim Kulac3, L. Nelleke Kisteman1, Lizamma Antony1, Hao Wang1, Alan K. Meeker1,3,4, Angelo M. De Marzo1,3,4, Isla P. Garraway2, Samuel R. Denmeade1,4 and John T. Isaacs1,4

1 Department of Oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA

2 Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

3 Department of Pathology at the SKCCC at Johns Hopkins, Baltimore, MD, USA

4 Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Correspondence to:

W. Nathaniel Brennen, email:

John T. Isaacs, email:

Keywords: mesenchymal stem cells, prostate cancer, benign prostatic hyperplasia, stem/progenitor cell, tissue-specific stem cell

Received: December 10, 2016 Accepted: April 01, 2017 Published: April 21, 2017

Abstract

Mesenchymal Stem Cells (MSCs) have been identified in prostate cancer, raising the critical question of their physical and temporal source. Therefore, MSCs were quantified and characterized in benign and malignant prostate tissue representing different disease states and a wide range of age groups from fetal development through adult death using analytical and functional methodologies. In contrast to lineage-restricted Mesenchymal Progenitor Cells (MPCs) found in normal prostate tissue, MSCs with tri-lineage differentiation potential (adipogenesis, osteogenesis, and chondrogenesis) are identified in prostate tissue from a subset of men with prostate cancer, consistent with an influx of more stem-like progenitors (i.e. MSCs) from the bone marrow. Additionally, prostate tissue from a subset of these patients is highly enriched in MSCs, suggesting their enumeration may have prognostic value for identifying men with aggressive disease. This influx is an ongoing process continuing throughout disease progression as documented by the presence of MSCs in metastatic lesions from multiple organ sites harvested at the time of death in metastatic castration-resistant prostate cancer (mCRPC) patients. This infiltration of MSCs from systemic circulation provides the rationale for their use as a cell-based vector to deliver therapeutic agents.


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