Brief report: A bioassay to identify primary human prostate cancer repopulating cells

Roxanne Toivanen, David M. Berman, Hong Wang, John Pedersen, Mark Frydenberg, Alan K. Meeker, Stuart J. Ellem, Gail P. Risbridger, Renea A. Taylor

Research output: Contribution to journalArticlepeer-review

Abstract

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 hiand 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.

Original languageEnglish (US)
Pages (from-to)1310-1314
Number of pages5
JournalStem Cells
Volume29
Issue number8
DOIs
StatePublished - Aug 2011

Keywords

  • Cancer
  • Experimental models
  • Immune-deficient models
  • Stromal cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Brief report: A bioassay to identify primary human prostate cancer repopulating cells'. Together they form a unique fingerprint.

Cite this