title: Prominin-1 (CD133, AC133) and dipeptidyl-peptidase IV (CD26) are indicators of infinitive growth in colon cancer cells.
abstract: Advanced colorectal cancer is characterized by uncontrolled growth and resistance against anti-cancer agents, including ErbB inhibitors. Recent data suggest that cancer stem cells (CSC) are particularly resistant. These cells may reside within a CD133+ fraction of the malignant cells. Using HCT116 cells we explored the role of CD133 and other CSC markers in drug resistance in colon cancer cells. CD133+ cells outnumbered CD133- cells over time in long-term culture. Both populations displayed the KRAS mutation 38G > A and an almost identical target profile, including EGFR/ErbB1, ErbB2, and ErbB4. Microarray analyses and flow cytometry identified CD26 as additional CSC marker co-expressed on CD133+ cells. However, knock-down of CD133 or CD26 did not affect short-term growth of HCT116 cells, and both cell-populations were equally resistant to various targeted drugs except irreversible ErbB inhibitors, which blocked growth and ERK1/2 phosphorylation in CD133- cells more efficiently than in CD133+ cells. Moreover, the MEK inhibitor AS703026 was found to overcome resistance against ErbB blockers in CD133+ cells. Together, CD133 and CD26 are markers of long-term growth and resistance to ErbB blockers in HCT116 cells, which may be mediated by constitutive ERK activity.
authors.affiliation: Ludwig Boltzmann Cluster Oncology, Medical University of Vienna Waehringer Guertel 18-20, A-1090 Vienna, Austria ; Division of Oncology, Department of Medicine I, Medical University of Vienna Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Grunt
authors.affiliation: Ludwig Boltzmann Cluster Oncology, Medical University of Vienna Waehringer Guertel 18-20, A-1090 Vienna, Austria ; Department of Radiotherapy, Medical University of Vienna Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hebar
authors.affiliation: Ludwig Boltzmann Cluster Oncology, Medical University of Vienna Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Laffer
authors.affiliation: Division of Oncology, Department of Medicine I, Medical University of Vienna Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Renate
authors.initials: R
authors.lastname: Wagner
authors.affiliation: Ludwig Boltzmann Cluster Oncology, Medical University of Vienna Waehringer Guertel 18-20, A-1090 Vienna, Austria ; Department of Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Peter
authors.affiliation: Ludwig Boltzmann Cluster Oncology, Medical University of Vienna Waehringer Guertel 18-20, A-1090 Vienna, Austria ; Department of Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Herrmann
authors.affiliation: Section of Medical Statistics, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Graf
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Bilban
authors.affiliation: Section of Medical Statistics, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Posch
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Gregor
authors.initials: G
authors.lastname: Hoermann
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mayerhofer
authors.affiliation: Ludwig Boltzmann Cluster Oncology, Medical University of Vienna Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Gregor
authors.initials: G
authors.lastname: Eisenwort
authors.affiliation: Ludwig Boltzmann Cluster Oncology, Medical University of Vienna Waehringer Guertel 18-20, A-1090 Vienna, Austria ; Division of Oncology, Department of Medicine I, Medical University of Vienna Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Christoph C
authors.initials: CC
authors.lastname: Zielinski
authors.affiliation: Ludwig Boltzmann Cluster Oncology, Medical University of Vienna Waehringer Guertel 18-20, A-1090 Vienna, Austria ; Department of Radiotherapy, Medical University of Vienna Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Edgar
authors.initials: E
authors.lastname: Selzer
authors.affiliation: Ludwig Boltzmann Cluster Oncology, Medical University of Vienna Waehringer Guertel 18-20, A-1090 Vienna, Austria ; Department of Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
keywords: CD133; CD26; Cancer stem cell; DPPIV; EGFR/ErbB; HCT116; colon cancer; drug resistance