ORCID Profile
0000-0003-1607-9035
Current Organisation
University of York
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Springer Science and Business Media LLC
Date: 04-04-2013
Abstract: Most cases of prostate cancer are now diagnosed as moderate-grade localized disease. These tumor specimens are important tools in the discovery and translation of prostate cancer research however, unlike more advanced tumors, they are notoriously difficult to grow in the laboratory. We developed a system for efficiently xenografting localized human prostate cancer tissue, and we adapted this protocol to study the interactions between the specific subsets of epithelial and stromal cells. Fresh prostate tissues or isolated epithelial cells are recombined with mouse seminal vesicle mesenchyme (SVM) and grafted under the renal capsule of immunodeficient mice for optimum growth and survival. Alternatively, mouse mesenchyme can be replaced with human prostate fibroblasts in order to determine their contribution to tumor progression. Grafts can be grown for several months to determine the effectiveness of novel therapeutic compounds when administered to host mice, thereby paving the way for personalizing the treatment of in idual prostate cancers.
Publisher: Springer Science and Business Media LLC
Date: 24-01-2014
DOI: 10.1038/CDD.2013.202
Publisher: Oxford University Press (OUP)
Date: 15-05-2012
DOI: 10.1002/STEM.1094
Abstract: Normal prostatic epithelium is composed of basal and luminal cells. Prostate cancer can be initiated in both benign basal and luminal stem cells, but because basal cell markers are not expressed in patient tumors, the former result was unexpected. Since the cells of origin of prostate cancer are important therapeutic targets, we sought to provide further proof that basal stem cells have tumorigenic potential. Prostatic basal cells were enriched based on α2β1integrinhi expression and further enriched for stem cells using CD133 in nontumorigenic BPH-1 cells. Human embryonic stem cells (hESCs) were also used as a source of normal stem cells. To test their tumorigenicity, we used two alternate stromal-based approaches (a) recombination with human cancer-associated fibroblasts (CAFs) or (b) recombination with embryonic stroma (urogenital mesenchyme) and treated host mice with testosterone and 17β-estradiol. Enriched α2β1integrinhi basal cells from BPH-1 cells resulted in malignant tumor formation using both assays of tumorigenicity. Surprisingly, the tumorigenic potential did not reside in the CD133+ stem cells but was consistently observed in the CD133− population. CAFs also failed to induce prostatic tumors from hESCs. These data confirmed that benign human basal cells include cells of origin of prostate cancer and reinforced their importance as therapeutic targets. In addition, our data suggested that the more proliferative CD133− basal cells are more susceptible to tumorigenesis compared to the CD133+-enriched stem cells. These findings challenge the current dogma that normal stem cells and cells of origin of cancer are the same cell type(s). Disclosure of potential conflicts of interest is found at the end of this article.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Norman Maitland.