| dc.description.abstract | Tumors contain a small subpopulation of cancer-initiating cells, known as cancer stem cells (CSCs) that exhibit a self-renewing capacity and are responsible for tumor generation. Cancer-initiating cells (CSCs) are the cells which would form tumors while having stem cell properties. It is suggested that CSCs persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors. Specific surface markers for colon CSCs have been reported, and CD133 is the most studied surface marker for colon CSCs. Several other colon CSC markers have been proposed; these include: ESA, CD44, CD166, Msi-1, CD29, CD24, Lgr5, and ALDH-1. However, exact and reliable surface markers of colon CSCs have not yet been identified rationally. The only reliable method for identifying and quantifying CSCs is the observation of tumor formation in a serial xenotransplantation model.
In this study, The drug-resistance cells of human colorectal adenocarcinoma tumor (LoVo) cells were found to produce more than two order higher amount of carcinoembryonic antigen (CEA) per cell, when less than 1% of the cells were survived in serum free medium or serum medium because of addition of anticancer drugs (5-FU, aspirin, oxaliplatin, cisplatin, Rosewell Park regime, or Mayo Clinic regime) in the culture medium. Drug-resistant LoVo cells were analyzed to determine whether those cells had CSC characteristics, e.g., small size of the cells/colonosphere and strong expression of CSC surface markers, as indicated by flow cytometry and immunohistochemistry analysis. Finally, in vivo tumorigenesis was examined by subcutaneously xenotransplanting the isolated drug-resistant LoVo cells into mice; we then evaluated whether the drug-resistant cells isolated in this study were CSCs. We found that drug-resistant cells, which comprised less than 1% of the LoVo human colon cancer cells that survived in serum-free or serum-containing medium supplemented with drugs (5-fluorouracil, acetylsalicylic acid, oxaliplatin, and cisplatin) were found to produce more than two orders higher than normal levels of carcinoembryonic antigen (CEA) per cell.
These results raised the question of whether CSCs could be isolated from drug-resistant colon cancer cells when anticancer drugs are added to the culture medium. The percentage of cells positive for CD133, which is known to be a typical marker of CSCs, decreased in parallel with a decrease in the cell survival rate after the addition of anticancer drugs in both the serum-free and serum-containing media. Drug-resistant LoVo cells had lower expression of CSC markers, including CD29, CD44, CD166, ALDH-1, Lgr5, and Msi-1, compared with the parental LoVo cells based on immunohistochemical examination.
It was concluded that the drug resistance cells of colon cancer cell line, which were isolated by addition of anticancer drugs in culture medium could enhance production of CEA in both serum free medium and serum medium, but were found not to be CSCs from tumor generation experiments in vivo, although CSCs were believed to be drug resistance cells in general. | en_US |