title: Identification of CD166 as a surface marker for enriching prostate stem/progenitor and cancer initiating cells.
abstract: New therapies for late stage and castration resistant prostate cancer (CRPC) depend on defining unique properties and pathways of cell sub-populations capable of sustaining the net growth of the cancer. One of the best enrichment schemes for isolating the putative stem/progenitor cell from the murine prostate gland is Lin(-);Sca1(+);CD49f(hi) (LSC(hi)), which results in a more than 10-fold enrichment for in vitro sphere-forming activity. We have shown previously that the LSC(hi) subpopulation is both necessary and sufficient for cancer initiation in the Pten-null prostate cancer model. To further improve this enrichment scheme, we searched for cell surface molecules upregulated upon castration of murine prostate and identified CD166 as a candidate gene. CD166 encodes a cell surface molecule that can further enrich sphere-forming activity of WT LSC(hi) and Pten null LSC(hi). Importantly, CD166 could enrich sphere-forming ability of benign primary human prostate cells in vitro and induce the formation of tubule-like structures in vivo. CD166 expression is upregulated in human prostate cancers, especially CRPC samples. Although genetic deletion of murine CD166 in the Pten null prostate cancer model does not interfere with sphere formation or block prostate cancer progression and CRPC development, the presence of CD166 on prostate stem/progenitors and castration resistant sub-populations suggest that it is a cell surface molecule with the potential for targeted delivery of human prostate cancer therapeutics.
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Jing
authors.initials: J
authors.lastname: Jiao
authors.forename: Antreas
authors.initials: A
authors.lastname: Hindoyan
authors.forename: Shunyou
authors.initials: S
authors.lastname: Wang
authors.forename: Linh M
authors.initials: LM
authors.lastname: Tran
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Goldstein
authors.forename: Devon
authors.initials: D
authors.lastname: Lawson
authors.forename: Donghui
authors.initials: D
authors.lastname: Chen
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Li
authors.forename: Changyong
authors.initials: C
authors.lastname: Guo
authors.forename: Baohui
authors.initials: B
authors.lastname: Zhang
authors.forename: Ladan
authors.initials: L
authors.lastname: Fazli
authors.forename: Martin
authors.initials: M
authors.lastname: Gleave
authors.forename: Owen N
authors.initials: ON
authors.lastname: Witte
authors.forename: Isla P
authors.initials: IP
authors.lastname: Garraway
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
mesh_terms: D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000378:metabolism*; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002369:Castration; D002462:Cell Membrane / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D012038:Regeneration; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: D020410:Activated-Leukocyte Cell Adhesion Molecule; D014408:Biomarkers, Tumor; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse