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Research Paper
Chemotherapy-Resistant Side-Population of Colon Cancer Cells has a Higher Sensitivity to TRAIL than the Non-SP, a Higher Expression of c-Myc and TRAIL-Receptor DR4
Robyn T. Sussman, M. Stacey Ricci, Lori S. Hart, Shi Yong Sun and Wafik S. El-Deiry
volume 6 | issue 9
September 2007Pages: 1490 - 1495
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Cancer stem cells are resistant to chemotherapy and provide an important target for drug development. We found that, surprisingly, the dye-effluxing side population (SP) within SW480 human colon tumor cells, a population defined to possess stem cell characteristics, expresses a 10-fold higher level of pro-apoptotic TRAIL receptor DR4 as compared to non-SP cells. The TRAIL receptors are activated by the anti-tumor host immune system through the TRAIL ligand. SW480 SP-cells express similar levels of another TRAIL receptor (DR5), as non-SP cells. SP-cells from multiple tumorigenic human cell lines, which are most often resistant to chemotherapeutic agents such as etoposide, cisplatin and 5-FU, are more sensitive to TRAIL than non-SP cells. SP-cells express higher levels of c-Myc than non-SP cells which may explain their sensitivity to TRAIL. We have found c-Myc activates DR4 transcription through E-box DNA-response elements located in the DR4 promoter, thereby increasing the expression of cell-surface pro-apoptotic death receptors in TRAIL-resistant cell lines. TRAIL sensitivity of SP-cells may represent a safeguard against malignancy, and therefore, offers a therapeutic window and opportunity.
Authors
Robyn T. Sussman
University of Pennsylvania School of Medicine, Philadelphia, PA
M. Stacey Ricci
University of Pennsylvania School of Medicine, Philadelphia, PA
Lori S. Hart
University of Pennsylvania School of Medicine, Philadelphia, PA
Shi Yong Sun
Emory Winship Cancer Institute, Atlanta, GA
Wafik S. El-Deiry
University of Pennsylvania School of Medicine; Philadelphia, PA
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.