The tumor stem cell theory supposed that tumor stem cells are the origin of tumor abnormal proliferation,invasion,metastasis,drug resistance and recurrence.As the theory is put forward,it redefines the functions of cl...The tumor stem cell theory supposed that tumor stem cells are the origin of tumor abnormal proliferation,invasion,metastasis,drug resistance and recurrence.As the theory is put forward,it redefines the functions of classic stem cells in tumorigenesis.It is a great event for recent studies on glioma initiating cells as brain tumor stem cells were identified and isolated successfully.A lot of evidence from experiments in vivo and in vitro demonstrates that brain tumor stem cells might play an important role in glioma tumorigenesis.In this review,we discuss the relationship between tumor stem cells and tumorigenesis,and the research on the correlation between brain tumor stem cells and glioma genesis.展开更多
Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are still unclear. In this study, we used stable doxycycline-inducible transgenic mou...Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are still unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models （c-myc/SV40Tag＋/Tet-on＋） to explore the malignant trans- formation potential of neural stem cells by observing the differences of neural stem cells and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain tumor stem cells. The numbers of cytolysosomes and autophagosomes in brain tumor stem cells and induced neural stem cells were lower and the proliferative activity was obviously stronger than that in normal neural stem cells. Normal neural stem cells could differentiate into glial fibrillary acidic protein-positive and microtubule associated protein-2-positive cells, which were also negative for nestin. However, glial fibrillary acidic protein/nestin, microtubule associated protein-2/nestin, and glial fibrillary acidic protein/microtubule associated protein-2 double-positive cells were found in induced neural stem cells and brain tumor stem cells. Results indicate that induced neural stem cells are similar to brain tumor stem cells, and are possibly the source of brain tumor stem cells.展开更多
Previous studies indicated that B7-H4,the youngest B7 family,negatively regulates T cell-mediated immunity and is significantly overexpressed in many human tumors.Tumor stem cells are purported to play a role in tumor...Previous studies indicated that B7-H4,the youngest B7 family,negatively regulates T cell-mediated immunity and is significantly overexpressed in many human tumors.Tumor stem cells are purported to play a role in tumor renewal and resistance to radiation and chemotherapy.However,the link between B7-H4and tumor stem cells is unclear.In this study,we investigated B7-H4 expression in the medium of human glioma U251 cell cultures.Immunofluorescence results showed that U251 cells cultured in serum-free medium(supplemented with 2%B27,20 ng/mL epidermal growth factor,20 ng/mL basic fibroblast growth factor)maintained stem-like cell characteristics,including expression of stem cell marker CD133 and the neural progenitor cell markers nestin and SOX2.In contrast,U251 cells cultured in serum-containing medium highly expressed differentiation marker glial fibrillary acidic protein.Flow cytometry analysis showed serum-free medium-cultured U251 cells expressed higher intracellular B7-H4 than serumcontaining medium-cultured U251 cells(24%-35%vs.8%-11%,P<0.001).Immunofluorescence in purified monocytes from normal human peripheral blood mononuclear cells revealed moderate expression of B7-H4 after stimulation with conditioned medium from U251 cells cultured in serum-containing medium.Moreover,conditioned medium from U251 stem-like cells had a significant stimulation effect on B7-H4expression compared with serum-containing conditioned medium(P<0.01).Negative costimulatory molecule B7-H4 was preferentially expressed in U251 stem-like cells,and conditioned medium from these cells more effectively induced monocytes to express B7-H4 than conditioned medium from U251 cells cultured in the presence of serum.Our results show that U251 stem-like cells may play a more crucial role in tumor immunoloregulation with high expression of B7-H4.展开更多
文摘The tumor stem cell theory supposed that tumor stem cells are the origin of tumor abnormal proliferation,invasion,metastasis,drug resistance and recurrence.As the theory is put forward,it redefines the functions of classic stem cells in tumorigenesis.It is a great event for recent studies on glioma initiating cells as brain tumor stem cells were identified and isolated successfully.A lot of evidence from experiments in vivo and in vitro demonstrates that brain tumor stem cells might play an important role in glioma tumorigenesis.In this review,we discuss the relationship between tumor stem cells and tumorigenesis,and the research on the correlation between brain tumor stem cells and glioma genesis.
文摘Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are still unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models （c-myc/SV40Tag＋/Tet-on＋） to explore the malignant trans- formation potential of neural stem cells by observing the differences of neural stem cells and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain tumor stem cells. The numbers of cytolysosomes and autophagosomes in brain tumor stem cells and induced neural stem cells were lower and the proliferative activity was obviously stronger than that in normal neural stem cells. Normal neural stem cells could differentiate into glial fibrillary acidic protein-positive and microtubule associated protein-2-positive cells, which were also negative for nestin. However, glial fibrillary acidic protein/nestin, microtubule associated protein-2/nestin, and glial fibrillary acidic protein/microtubule associated protein-2 double-positive cells were found in induced neural stem cells and brain tumor stem cells. Results indicate that induced neural stem cells are similar to brain tumor stem cells, and are possibly the source of brain tumor stem cells.
基金supported by grants from the National Natural Science Foundation of China (No.81272797 to Y.Y.)nnovation Program of Shanghai Municipal Education Commission (No.13ZZ010 to Y.Y.)Shanghai Talents Development Funds (No.2011063 to Y.Y.)
文摘Previous studies indicated that B7-H4,the youngest B7 family,negatively regulates T cell-mediated immunity and is significantly overexpressed in many human tumors.Tumor stem cells are purported to play a role in tumor renewal and resistance to radiation and chemotherapy.However,the link between B7-H4and tumor stem cells is unclear.In this study,we investigated B7-H4 expression in the medium of human glioma U251 cell cultures.Immunofluorescence results showed that U251 cells cultured in serum-free medium(supplemented with 2%B27,20 ng/mL epidermal growth factor,20 ng/mL basic fibroblast growth factor)maintained stem-like cell characteristics,including expression of stem cell marker CD133 and the neural progenitor cell markers nestin and SOX2.In contrast,U251 cells cultured in serum-containing medium highly expressed differentiation marker glial fibrillary acidic protein.Flow cytometry analysis showed serum-free medium-cultured U251 cells expressed higher intracellular B7-H4 than serumcontaining medium-cultured U251 cells(24%-35%vs.8%-11%,P<0.001).Immunofluorescence in purified monocytes from normal human peripheral blood mononuclear cells revealed moderate expression of B7-H4 after stimulation with conditioned medium from U251 cells cultured in serum-containing medium.Moreover,conditioned medium from U251 stem-like cells had a significant stimulation effect on B7-H4expression compared with serum-containing conditioned medium(P<0.01).Negative costimulatory molecule B7-H4 was preferentially expressed in U251 stem-like cells,and conditioned medium from these cells more effectively induced monocytes to express B7-H4 than conditioned medium from U251 cells cultured in the presence of serum.Our results show that U251 stem-like cells may play a more crucial role in tumor immunoloregulation with high expression of B7-H4.
