
Переход карцином в Ñтадию метаÑÑ‚Ð°Ð·Ð¸Ñ€Ð¾Ð²Ð°Ð½Ð¸Ñ Ð¼Ð¾Ð¶ÐµÑ‚ быть оÑущеÑтвлен Ñ Ð¿Ð¾Ð¼Ð¾Ñ‰ÑŒÑŽ программы Ñпителиально-мезенхимального перехода (ÐМП). Ð’ данной работе было изучено влиÑние ÐМП на характериÑтики наиболее агреÑÑивной популÑции опухолевых клеток – опухолевых Ñтволовых клеток (ОСК). ПоÑредÑтвом Ð²Ð²ÐµÐ´ÐµÐ½Ð¸Ñ Ð¿Ð»Ð°Ð·Ð¼Ð¸Ð´Ð½Ð¾Ð¹ конÑтрукции, Ñодержащей клонированный ZEB1, был индуцирован ÐМП. Отбор Ñтволового компонента оÑущеÑтвлÑлÑÑ Ñ Ð¿Ð¾Ð¼Ð¾Ñ‰ÑŒÑŽ репортерной конÑтрукции, Ñодержащей Ñайты ÑвÑÐ·Ñ‹Ð²Ð°Ð½Ð¸Ñ OCT4/SOX2. Методом ОТ-ПЦРв реальном времени были получены уровни мРÐК оÑновных маркеров ОСК. Уровни мРÐК данных маркеров в клоне Ñ Ð¸Ð½Ð´ÑƒÑ†Ð¸Ñ€Ð¾Ð²Ð°Ð½Ð½Ñ‹Ð¼ ÐМП были в неÑколько раз выше, чем в обычном Ñтволовом компоненте. ÐеÑÐ¼Ð¾Ñ‚Ñ€Ñ Ð½Ð° превышение уровней мРÐК транÑкрипционных факторов TWIST и SNAIL, отвечающих за активацию ÐМП, в Ñтволовом компоненте клеток не было выÑвлено отличий в уровнÑÑ… мРÐК ZEB1, виментина и Е-кадгерина, оÑновных маркеров ÐМП. Ð’ то же Ð²Ñ€ÐµÐ¼Ñ Ð²Ñ‹Ñвлены Ð¾Ñ‚Ð»Ð¸Ñ‡Ð¸Ñ Ð² морфологии и миграционной ÑпоÑобноÑти клеток «подобных Ñтволовым». Таким образом, можно заключить, что введение ZEB1 в клетки колоректального рака привело к получению клонов, не только характеризующихÑÑ Ð¿Ð¾Ð²Ñ‹ÑˆÐµÐ½Ð½Ñ‹Ð¼Ð¸ уровнÑми маркеров ОСК, но и ÑпоÑобных к миграции.
The epithelial-mesenchymal transition is the main program that is responsible for metastasis. The given work is devoted to the exploration of the induced epithelial-mesenchymal transition (EMT) on cancer stem-like cells (CSC) influence, which are the most aggressive members of the cancer cells population. We used a special plasmid, which contains the ZEB1 gene, to induce the EMT program in the colorectal cancer cell line MIP101. The population of cancer stem-like cells was selected using construction with six binding sites for OCT4/SOX2 transcription factors. We have used the real-time RT-PСR method to examine the main CSC marker’s mRNA levels. We noticed that mRNA levels of these markers in cancer stem-like cells with induced EMT was higher than in the control group of cancer stem-like cells. Also, we noticed that high mRNA levels of transcriptional factors such as TWIST and SNAIL, which are involved in EMT, had not affected the mRNA levels of ZEB1, vimentin and E-cadherin, which are the EMT markers. On the other hand, there were some differences in morphology and migration ability of cancer like-stem cells under EMT and control group. Thus, it can be concluded that ZEB1 transfection in colorectal cancer cells can lead to increased levels of CSC’s markers as well as high migration ability.
cancer stem cells, tumorigenesis, колоÑекÑалÑнÑй Ñак, transcription factors, ÑÑанÑкÑипÑионнÑе ÑакÑоÑÑ, epithelial-mesenchymal transition, ÑпиÑелиалÑно-Ð¼ÐµÐ·ÐµÐ½Ñ Ð¸Ð¼Ð°Ð»ÑнÑй пеÑÐµÑ Ð¾Ð´, colorectal cancer, опÑÑ Ð¾Ð»ÐµÐ²Ñе ÑÑволовÑе клеÑки, канÑеÑогенез
cancer stem cells, tumorigenesis, колоÑекÑалÑнÑй Ñак, transcription factors, ÑÑанÑкÑипÑионнÑе ÑакÑоÑÑ, epithelial-mesenchymal transition, ÑпиÑелиалÑно-Ð¼ÐµÐ·ÐµÐ½Ñ Ð¸Ð¼Ð°Ð»ÑнÑй пеÑÐµÑ Ð¾Ð´, colorectal cancer, опÑÑ Ð¾Ð»ÐµÐ²Ñе ÑÑволовÑе клеÑки, канÑеÑогенез
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