Oxaliplatin and irinotecan induce heterogenous changes in the EMT markers of metastasizing colorectal carcinoma cells
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
29842879
DOI
10.1016/j.yexcr.2018.05.032
PII: S0014-4827(18)30303-3
Knihovny.cz E-resources
- Keywords
- ABCATP binding cassette, CRCColorectal cancer, Drug resistance, EMTEpithelial-mesenchymal transition, Epithelial-mesenchymal transition, ITIrinotecan, Irinotecan, MRPMultidrug resistance-associated protein, Metastatic colon cancer, OPTOxaliplatin, Oxaliplatin, Primary cell lines,
- MeSH
- Adenocarcinoma drug therapy metabolism secondary MeSH
- Antineoplastic Agents pharmacology MeSH
- Drug Resistance, Neoplasm MeSH
- Epithelial-Mesenchymal Transition drug effects MeSH
- Neoplasm Invasiveness MeSH
- Irinotecan pharmacology MeSH
- Colorectal Neoplasms drug therapy metabolism pathology MeSH
- Humans MeSH
- Lymphatic Metastasis MeSH
- Biomarkers, Tumor genetics metabolism MeSH
- Cell Line, Tumor MeSH
- Oxaliplatin pharmacology MeSH
- Neovascularization, Pathologic MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antineoplastic Agents MeSH
- Irinotecan MeSH
- Biomarkers, Tumor MeSH
- Oxaliplatin MeSH
In patients with advanced colorectal cancer (CRC), surgery is complemented with systemic therapy - chemotherapy and radiochemotherapy. Although the patients' overall survival has been significantly improved, tumor resistance is still a frequent cause of chemotherapy failure. Several factors contribute to chemoresistance of tumor cells including changes related with epithelial-mesenchymal transition (EMT). The present study was designed to verify the presence of EMT markers in paired CRC primary cell lines obtained from primary tumor sites and lymph node metastases of three patients and to investigate the effect of irinotecan and oxaliplatin treatment on these markers as well. The samples of the higher stage of CRC and positive for angioinvasion were selected and qPCR, western blot analysis, migration assay, cytotoxicity testing was performed. Results confirmed the increased expression of several markers characteristic of EMT and invasiveness in lymph node metastatic cells, with a significant variability between individual samples. Irinotecan and oxaliplatin decreased migration activity of the cells and to the varying degree affected the expression of EMT and invasiveness markers. In conclusion, in CRC EMT is present in metastatic cells over a phenotypic continuum whose expression is altered heterogeneously upon irinotecan and oxaliplatin treatment.
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