Prominin-1 (CD133, AC133) and dipeptidyl-peptidase IV (CD26) are indicators of infinitive growth in colon cancer cells

• Published in: American journal of cancer research Vol. 5; no. 2; pp. 560 - 574
• Main Authors: Grunt, Thomas W, Hebar, Alexandra, Laffer, Sylvia, Wagner, Renate, Peter, Barbara, Herrmann, Harald, Graf, Alexandra, Bilban, Martin, Posch, Martin, Hoermann, Gregor, Mayerhofer, Matthias, Eisenwort, Gregor, Zielinski, Christoph C, Selzer, Edgar, Valent, Peter
• Format: Journal Article
• Language: English
• Published: United States e-Century Publishing Corporation 01.01.2015
• Subjects: Original; EGFR/ErbB; DPPIV; colon cancer; Cancer stem cell; HCT116; CD26; drug resistance; CD133
• ISSN: 2156-6976; 2156-6976

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.