American journal of cancer research. 2015 Jan 15. pmc: PMC4396035 |
Prominin-1 (CD133, AC133) and dipeptidyl-peptidase IV (CD26) are indicators of infinitive growth in colon cancer cells. |
Grunt TW1, Hebar A2, Laffer S3, Wagner R4, Peter B5, Herrmann H6, Graf A7, Bilban M8, Posch M9, Hoermann G10, Mayerhofer M11, Eisenwort G12, Zielinski CC13, Selzer E14, Valent P15 |
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. |
KEYWORDS: CD133, CD26, Cancer stem cell, DPPIV, EGFR/ErbB, HCT116, colon cancer, drug resistance |
Publikations ID: 25973297 Quelle: öffnen |