title: Identification of CBX3 and ABCA5 as putative biomarkers for tumor stem cells in osteosarcoma.
abstract: Recently, there has been renewed interest in the role of tumor stem cells (TSCs) in tumorigenesis, chemoresistance, and relapse of malignant tumors including osteosarcoma. The potential exists to improve osteosarcoma treatment through characterization of TSCs and identification of therapeutic targets. Using transcriptome, proteome, immunophenotyping for cell-surface markers, and bioinformatic analyses, heterogeneous expression of previously reported TSC or osteosarcoma markers, such as CD133, nestin, POU5F1 (OCT3/4), NANOG, SOX2, and aldehyde dehydrogenase, among others, was observed in vitro. However, consistently significantly lower CD326, CD24, CD44, and higher ABCG2 expression in TSC-enriched as compared with un-enriched osteosarcoma cultures was observed. In addition, consistently higher CBX3 expression in TSC-enriched osteosarcoma cultures was identified. ABCA5 was identified as a putative biomarker of TSCs and/or osteosarcoma. Lastly, in a high-throughput screen we identified epigenetic (5-azacytidine), anti-microtubule (vincristine), and anti-telomerase (3,11-difluoro-6,8,13-trimethyl- 8H-quino [4,3,2-kl] acridinium methosulfate; RHPS4)-targeted therapeutic agents as candidates for TSC ablation in osteosarcoma.
authors.affiliation: Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute at Frederick, Frederick, Maryland, United States of America.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Saini
authors.forename: Curtis D
authors.initials: CD
authors.lastname: Hose
authors.forename: Anne
authors.initials: A
authors.lastname: Monks
authors.forename: Kunio
authors.initials: K
authors.lastname: Nagashima
authors.forename: Bingnan
authors.initials: B
authors.lastname: Han
authors.forename: Dianne L
authors.initials: DL
authors.lastname: Newton
authors.forename: Angelena
authors.initials: A
authors.lastname: Millione
authors.forename: Jalpa
authors.initials: J
authors.lastname: Shah
authors.forename: Melinda G
authors.initials: MG
authors.lastname: Hollingshead
authors.forename: Karen M
authors.initials: KM
authors.lastname: Hite
authors.forename: Mark W
authors.initials: MW
authors.lastname: Burkett
authors.forename: Rene M
authors.initials: RM
authors.lastname: Delosh
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Silvers
authors.forename: Dominic A
authors.initials: DA
authors.lastname: Scudiero
authors.forename: Robert H
authors.initials: RH
authors.lastname: Shoemaker
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D001374:Azacitidine / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis*; D005266:Femoral Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D014750:Vincristine / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C471294:ABCA5 protein, human; D018528:ATP-Binding Cassette Transporters; D014408:Biomarkers, Tumor; C518294:CBX3 protein, human; D002868:Chromosomal Proteins, Non-Histone; D009363:Neoplasm Proteins; D014750:Vincristine; D001374:Azacitidine