ABSTRACT
In the current work we make an attempt to compare cancer cells of one origin, but differing in the expression of CEA protein, a clinical marker of metastatic carcinomas, presumably one of the key factors in metastatic activity. We have explored the morphology of cell colonies in vitro, expression patterns of epithelial markers, the ability of these cells to form tumors and metastases in vivo, and evaluated their stem compartment with the aid of a suicidal genetic construct sensitive to the embryonic stem cell marker, Oct4.
Subject(s)
Biomarkers, Tumor/genetics , Colorectal Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Liver Neoplasms/secondary , Neoplastic Stem Cells/pathology , Octamer Transcription Factor-3/genetics , Animals , Biomarkers, Tumor/metabolism , Cell Line, Tumor , Clone Cells , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Genetic Vectors , HEK293 Cells , Humans , Lentivirus/genetics , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Mice , Mice, Nude , Neoplasm Invasiveness , Neoplasm Transplantation , Neoplastic Stem Cells/metabolism , Octamer Transcription Factor-3/metabolism , Tumor BurdenABSTRACT
In present publication we describe for the first time the obtainment of cancer stem cells from a weakly metastatic human colorectal carcinoma cell line MIP101 via selecting from the native population the cells that express intensively an embryonic stem cell marker, POU5F1 (Oct4). We provide the evidence that these cells possess an elevated clonogenic and tumorigenic potential when compared to the native population, and this correlates to the hypothesis of cancer stem cells' primary role in the development of malignant neoplasms.
Subject(s)
Colorectal Neoplasms/genetics , Embryonic Stem Cells/cytology , Neoplastic Stem Cells/cytology , Octamer Transcription Factor-3/biosynthesis , Animals , Biomarkers, Tumor/genetics , Cell Line, Tumor , Cell Lineage/genetics , Colorectal Neoplasms/etiology , Colorectal Neoplasms/pathology , Embryonic Stem Cells/metabolism , Gene Expression Regulation, Neoplastic , Humans , Mice , Neoplasm Metastasis/genetics , Neoplasm Metastasis/pathology , Neoplastic Stem Cells/metabolismABSTRACT
Induced pluripotent stem (iPS) cells are derived from somatic cells reprogrammed to the pluripotent state by the induced expression of defined transcription factors, achieved for the first time by the seminal work of Takahashi and Yamanaka. This new type of pluripotent cells has offered new exciting options in regenerative medicine allowing the replacement of cells and organs with the patient's own cells thereby avoiding immunological complications. In order to develop such technologies in approved animal models, iPS cells were also generated from rodents. Of course, the most important model for studying of different diseases is rat. In this study, we present a method suitable for rat iPS cells genetic modification by stable transfection and show necessary conditions for the first stages of direct differentiation.