title: Brief report: a bioassay to identify primary human prostate cancer repopulating cells.
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(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.
authors.affiliation: Prostate and Breast Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Roxanne
authors.initials: R
authors.lastname: Toivanen
authors.forename: David M
authors.initials: DM
authors.lastname: Berman
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: John
authors.initials: J
authors.lastname: Pedersen
authors.forename: Mark
authors.initials: M
authors.lastname: Frydenberg
authors.forename: Alan K
authors.initials: AK
authors.lastname: Meeker
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Ellem
authors.forename: Gail P
authors.initials: GP
authors.lastname: Risbridger
authors.forename: Renea A
authors.initials: RA
authors.lastname: Taylor
mesh_terms: D000368:Aged; D000818:Animals; D000831:Animals, Newborn; D001681:Biological Assay / Q000379:methods*; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism; D008297:Male; D008648:Mesoderm / Q000473:pathology / Q000637:transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009368:Neoplasm Transplantation / Q000379:methods; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014183:Transplantation, Heterologous / Q000379:methods
chemical_list: D038982:Integrin alpha2beta1