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Single-cell clones of liver cancer stem cells have the potential of differentiating into different types of tumor cells.

Liu H, Zhang W, Jia Y, Yu Q, Grau GE, Peng L, Ran Y, Yang Z, Deng H, Lou J - Cell Death Dis (2013)

Bottom Line: Here, we show that single-cell-cloned CSCs, accidentally obtained from a human liver cancer microvascular endothelial cells, express classic stem cell markers, genes associated with self-renewal and pluripotent factors and possess colony-forming ability in vitro and the ability of serial transplantation in vivo.Interestingly, this multilineage differentiation potential of single-cell-cloned liver CSCs sharply declined after the specific knockdown of octamer-binding transcription factor 4 (Oct4) alone, even though they were under the same induction conditions (carcinoma microenvironments).Simultaneously, Oct4 in CSCs is indispensable in this process.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, PR China.

ABSTRACT
Cancer stem cells (CSCs) are believed to be a promising target for cancer therapy because these cells are responsible for tumor development, maintenance and chemotherapy resistance. Finding out the critical factors regulating CSC fate is the key for target therapy of CSCs. Just as normal stem cells are regulated by their microenvironment (niche), CSCs are also regulated by cells in the tumor microenvironment. However, whether various tumor microenvironments can induce CSCs to differentiate into different cancer cells is not clear. Here, we show that single-cell-cloned CSCs, accidentally obtained from a human liver cancer microvascular endothelial cells, express classic stem cell markers, genes associated with self-renewal and pluripotent factors and possess colony-forming ability in vitro and the ability of serial transplantation in vivo. The single-cell-cloned CSCs treated with the different tumor cell/tissue-derived conditioned culture medium, which is a mimic of carcinoma microenvironment, could differentiate into corresponding tumor cells and express specific markers of the respective type of tumor cells at the gene, protein and cell levels, respectively. Interestingly, this multilineage differentiation potential of single-cell-cloned liver CSCs sharply declined after the specific knockdown of octamer-binding transcription factor 4 (Oct4) alone, even though they were under the same induction conditions (carcinoma microenvironments). These data support the hypothesis that single-cell-cloned liver CSCs have the potential of differentiating into different types of tumor cells, and the tumor microenvironment does play a crucial role in deciding differentiation directions. Simultaneously, Oct4 in CSCs is indispensable in this process. These factors are promising targets for liver CSC-specific therapy.

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Related in: MedlinePlus

Generation of the T3A-A3 cells. (a) Single-cell clone screening of T3A cells by limiting-dilution assay. (b) Compared with the proliferation rate of 20 clones in vitro by MTT assay. (c) Compared the tumorigenicity of high and low proliferation rate clones in SCID mice
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fig2: Generation of the T3A-A3 cells. (a) Single-cell clone screening of T3A cells by limiting-dilution assay. (b) Compared with the proliferation rate of 20 clones in vitro by MTT assay. (c) Compared the tumorigenicity of high and low proliferation rate clones in SCID mice

Mentions: Single-cell-cloning origin is the premise to study the multilineage differentiation potential of stem cells. To this end, T3A cells were plated in a 96-well plate for single-cell sorting by limiting dilution (Figure 2a). It is important to note that T3A cells consist of heterogeneous populations of cells. The majority of single cells have limited proliferative potential, whereas only a small fraction has the capacity to persist long term and has unlimited proliferative capacity. We eventually have gained 20 clones. The 20 clones are unequal. The MTT assay (Figure 2b) shows that their proliferation rates vary.


Single-cell clones of liver cancer stem cells have the potential of differentiating into different types of tumor cells.

Liu H, Zhang W, Jia Y, Yu Q, Grau GE, Peng L, Ran Y, Yang Z, Deng H, Lou J - Cell Death Dis (2013)

Generation of the T3A-A3 cells. (a) Single-cell clone screening of T3A cells by limiting-dilution assay. (b) Compared with the proliferation rate of 20 clones in vitro by MTT assay. (c) Compared the tumorigenicity of high and low proliferation rate clones in SCID mice
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3824650&req=5

fig2: Generation of the T3A-A3 cells. (a) Single-cell clone screening of T3A cells by limiting-dilution assay. (b) Compared with the proliferation rate of 20 clones in vitro by MTT assay. (c) Compared the tumorigenicity of high and low proliferation rate clones in SCID mice
Mentions: Single-cell-cloning origin is the premise to study the multilineage differentiation potential of stem cells. To this end, T3A cells were plated in a 96-well plate for single-cell sorting by limiting dilution (Figure 2a). It is important to note that T3A cells consist of heterogeneous populations of cells. The majority of single cells have limited proliferative potential, whereas only a small fraction has the capacity to persist long term and has unlimited proliferative capacity. We eventually have gained 20 clones. The 20 clones are unequal. The MTT assay (Figure 2b) shows that their proliferation rates vary.

Bottom Line: Here, we show that single-cell-cloned CSCs, accidentally obtained from a human liver cancer microvascular endothelial cells, express classic stem cell markers, genes associated with self-renewal and pluripotent factors and possess colony-forming ability in vitro and the ability of serial transplantation in vivo.Interestingly, this multilineage differentiation potential of single-cell-cloned liver CSCs sharply declined after the specific knockdown of octamer-binding transcription factor 4 (Oct4) alone, even though they were under the same induction conditions (carcinoma microenvironments).Simultaneously, Oct4 in CSCs is indispensable in this process.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, PR China.

ABSTRACT
Cancer stem cells (CSCs) are believed to be a promising target for cancer therapy because these cells are responsible for tumor development, maintenance and chemotherapy resistance. Finding out the critical factors regulating CSC fate is the key for target therapy of CSCs. Just as normal stem cells are regulated by their microenvironment (niche), CSCs are also regulated by cells in the tumor microenvironment. However, whether various tumor microenvironments can induce CSCs to differentiate into different cancer cells is not clear. Here, we show that single-cell-cloned CSCs, accidentally obtained from a human liver cancer microvascular endothelial cells, express classic stem cell markers, genes associated with self-renewal and pluripotent factors and possess colony-forming ability in vitro and the ability of serial transplantation in vivo. The single-cell-cloned CSCs treated with the different tumor cell/tissue-derived conditioned culture medium, which is a mimic of carcinoma microenvironment, could differentiate into corresponding tumor cells and express specific markers of the respective type of tumor cells at the gene, protein and cell levels, respectively. Interestingly, this multilineage differentiation potential of single-cell-cloned liver CSCs sharply declined after the specific knockdown of octamer-binding transcription factor 4 (Oct4) alone, even though they were under the same induction conditions (carcinoma microenvironments). These data support the hypothesis that single-cell-cloned liver CSCs have the potential of differentiating into different types of tumor cells, and the tumor microenvironment does play a crucial role in deciding differentiation directions. Simultaneously, Oct4 in CSCs is indispensable in this process. These factors are promising targets for liver CSC-specific therapy.

Show MeSH
Related in: MedlinePlus