The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
CD44‐positive cells are responsible for gemcitabine resistance in pancreatic cancer cells
Open accessAbstract
Accumulating evidence suggests that tumors are composed of a heterogeneous cell population with a small subset of cancer stem cells (CSCs) that sustain tumor formation and growth. Recently, there have been efforts to explain drug resistance of cancer cells based on the concept of CSCs having an intrinsic detoxifying mechanism. In the present study, to investigate the role of CSCs in acquiring chemoresistance in pancreatic cancer, gemcitabine‐resistant cells were established by exposure to serially escalated doses of gemcitabine in HPAC and CFPAC‐1 cells. Gemcitabine‐resistant cells were more tumorigenic in vitro and in vivo, and had greater sphere‐forming activity than parental cells. After high‐dose gemcitabine treatment to eliminate most of the cells, CD44+ cells proliferated and reconstituted the population of resistant cells. CD44+CD24+ESA+ cells remained as a small subset in the resistant cell population. Among ATP‐binding cassette (ABC) transporters, which are known as the mechanism of drug resistance in CSCs, ABCB1 (MDR1) was significantly augmented during the acquisition of drug resistance. ABC transporter inhibitor verapamil resensitized the resistant cells to gemcitabine in a dose‐dependent manner and RNA interference of CD44 inhibited the clonogenic activity of resistant cells. In human pancreatic cancer samples, CD44 expression was correlated with histologic grade and the patients with CD44‐positive tumors showed poor prognosis. These data indicate that cancer stem‐like cells were expanded during the acquisition of gemcitabine resistance and in therapeutic application, targeted therapy against the CD44 or ABC transporter inhibitors could be applied to overcome drug resistance in the treatment of pancreatic cancer. © 2009 UICC
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Pancreatic cancer: understanding and overcoming chemoresistance
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Hu, Z. I., Bendell, J. C., Bullock, A., LoConte, N. K., Hatoum, H., Ritch, P., Hool, H., Leach, J. W., Sanchez, J., Sohal, D. P. S., et al. (2019) · Cancer Medicine · doi:10.1002/cam4.2425 · Cited by 82
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Qi, B., Crawford, A. J., Wojtynek, N. E., Talmon, G. A., Hollingsworth, M. A., Ly, Q. P., & Mohs, A. M. (2020) · Theranostics · doi:10.7150/thno.40688 · Cited by 18
Metadata
- Authors
- Hong, S. P., Wen, J., Bang, S., Park, S., & Song, S. Y.
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2009-09-18
- Volume
- 125
- Issue
- 10
- Pages
- 2323-2331
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W2037961348
- Cited by
- 290
- References
- 41
- FWCI
- 13.13
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Hong, S. P., Wen, J., Bang, S., Park, S., & Song, S. Y. (2009). CD44‐positive cells are responsible for gemcitabine resistance in pancreatic cancer cells. International Journal of Cancer. https://doi.org/10.1002/ijc.24573
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