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Brief Report: A Bioassay to Identify Primary Human Prostate Cancer Repopulating Cells
Author(s) -
Toivanen Roxanne,
Berman David M.,
Wang Hong,
Pedersen John,
Frydenberg Mark,
Meeker Alan K.,
Ellem Stuart J.,
Risbridger Gail P.,
Taylor Renea A.
Publication year - 2011
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.668
Subject(s) - mesenchyme , biology , cancer research , cancer , cancer cell , prostate cancer , transplantation , pathology , immunology , mesenchymal stem cell , medicine , microbiology and biotechnology , genetics
Cancer cells are heterogeneous in both their phenotypes and ability to promote tumor growth and spread. Xenografting is used to identify the most highly capable cells of regenerating tumors, referred to as cancer repopulating cells. Because prostate cancers (PCa's) rarely grow as xenografts, indentifying PCa repopulating cells has not been possible. Here, we report improved methods to xenograft localized primary PCa tissues using chimeric grafts with neonatal mouse mesenchyme. Xenograft survival of tumor tissue was significantly increased by neonatal mesenchyme (six of six patients, 66% of grafts, versus four of six patients, 41% of grafts) and doubled the proliferation index of xenografted cancer cells. When applied to isolated PCa cells, neonatal mesenchyme effectively reconstituted PCa's and increased xenograft survival (four of nine patients; 32% of grafts with mesenchyme and 0% without), and supported active cancer cell proliferation. Using this assay, we showed that unfractionated α2β1integrin hi and α2β1integrin lo cells from primary localized PCa's demonstrated tumor formation at comparable rates, similar to previous reports using metastatic specimens. Thus, this new protocol efficiently established tumors and enabled proliferative expansion of both intact tumor tissue and fractionated cancer cells, providing a bioassay to identify and therapeutically target PCa repopulating cells. S TEM C ELLS 2011;29:1310–1314

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