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Downregulation of transcription factor SOX2 in cancer stem cells suppresses growth and metastasis of lung cancer.

Xiang R, Liao D, Cheng T, Zhou H, Shi Q, Chuang TS, Markowitz D, Reisfeld RA, Luo Y - Br. J. Cancer (2011)

Bottom Line: In addition, the migration of D121-SP was decreased, and apoptosis of D121-SP was upregulated following knocking down of SOX2 in D121 cells.Importantly, downregulation of SOX2 in D121 cells markedly suppressed their metastatic potential in syngeneic mice.These results suggest that the SP is an enriched source of lung tumour cells with stem cell properties and that SOX2 has an important role in maintaining stem cell properties and functions that may be a potential target for effective lung cancer therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

ABSTRACT

Background: The cancer stem cell hypothesis suggests that neoplastic clones are maintained exclusively by a small subpopulation of cells, which have indefinite proliferation and differentiation potentials and give rise to phenotypically diverse cancer cells. Cancer stem cells have been isolated by their ability to efflux Hoechst 33342 dye and are referred to as the 'side population' (SP).

Methods and results: The Hoechst efflux assay was used to isolate and characterize the SP from murine D121 lung carcinoma cells. Here, we demonstrated that D121-SP cells contain cancer stem cell characteristics, that is, upregulation of the transcription factors SOX2 and Oct 4 in D121-SP cells. In addition, the migration of D121-SP was decreased, and apoptosis of D121-SP was upregulated following knocking down of SOX2 in D121 cells. Importantly, downregulation of SOX2 in D121 cells markedly suppressed their metastatic potential in syngeneic mice.

Conclusions: These results suggest that the SP is an enriched source of lung tumour cells with stem cell properties and that SOX2 has an important role in maintaining stem cell properties and functions that may be a potential target for effective lung cancer therapy.

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Upregulation of stem cell markers on D121-SP population. (A) Expressions of ABCG2 and Sca-1 stem cell markers were upregulated in the SP cells derived from D121 lung tumour cells as detected by flow cytometry, immunofluorescence histology staining (B) and RT–PCR (C).
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fig2: Upregulation of stem cell markers on D121-SP population. (A) Expressions of ABCG2 and Sca-1 stem cell markers were upregulated in the SP cells derived from D121 lung tumour cells as detected by flow cytometry, immunofluorescence histology staining (B) and RT–PCR (C).

Mentions: To further establish the characteristics of SP cells among D121 tumour cells, we analysed for the expression of markers known to be associated with stem or progenitor cells. To this end, we performed flow cytometry, immunohistochemical fluorescence staining and RT–PCR, respectively, to verify the expression of Sca-1 and ABCG2 by different methods. We found expression of ABCG2 and Sca-1 to be upregulated in the SP cells isolated from D121 lung cancer cells when compared with that of non-SP derived from these same cancer cells as detected by flow cytometry (Figure 2A), by immunohistochemical fluorescence histology staining (Figure 2B) and RT–PCR (Figure 2C). Together, these results demonstrate that D121-SP cells express the stem cell marker Sca-1 as well as the ABCG2 ATP-binding cassette transporter, which is associated with resistance to multiple chemotherapeutic drugs. These results support our contention that D121-SP cells have a stem cell gene expression profile.


Downregulation of transcription factor SOX2 in cancer stem cells suppresses growth and metastasis of lung cancer.

Xiang R, Liao D, Cheng T, Zhou H, Shi Q, Chuang TS, Markowitz D, Reisfeld RA, Luo Y - Br. J. Cancer (2011)

Upregulation of stem cell markers on D121-SP population. (A) Expressions of ABCG2 and Sca-1 stem cell markers were upregulated in the SP cells derived from D121 lung tumour cells as detected by flow cytometry, immunofluorescence histology staining (B) and RT–PCR (C).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3101944&req=5

fig2: Upregulation of stem cell markers on D121-SP population. (A) Expressions of ABCG2 and Sca-1 stem cell markers were upregulated in the SP cells derived from D121 lung tumour cells as detected by flow cytometry, immunofluorescence histology staining (B) and RT–PCR (C).
Mentions: To further establish the characteristics of SP cells among D121 tumour cells, we analysed for the expression of markers known to be associated with stem or progenitor cells. To this end, we performed flow cytometry, immunohistochemical fluorescence staining and RT–PCR, respectively, to verify the expression of Sca-1 and ABCG2 by different methods. We found expression of ABCG2 and Sca-1 to be upregulated in the SP cells isolated from D121 lung cancer cells when compared with that of non-SP derived from these same cancer cells as detected by flow cytometry (Figure 2A), by immunohistochemical fluorescence histology staining (Figure 2B) and RT–PCR (Figure 2C). Together, these results demonstrate that D121-SP cells express the stem cell marker Sca-1 as well as the ABCG2 ATP-binding cassette transporter, which is associated with resistance to multiple chemotherapeutic drugs. These results support our contention that D121-SP cells have a stem cell gene expression profile.

Bottom Line: In addition, the migration of D121-SP was decreased, and apoptosis of D121-SP was upregulated following knocking down of SOX2 in D121 cells.Importantly, downregulation of SOX2 in D121 cells markedly suppressed their metastatic potential in syngeneic mice.These results suggest that the SP is an enriched source of lung tumour cells with stem cell properties and that SOX2 has an important role in maintaining stem cell properties and functions that may be a potential target for effective lung cancer therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

ABSTRACT

Background: The cancer stem cell hypothesis suggests that neoplastic clones are maintained exclusively by a small subpopulation of cells, which have indefinite proliferation and differentiation potentials and give rise to phenotypically diverse cancer cells. Cancer stem cells have been isolated by their ability to efflux Hoechst 33342 dye and are referred to as the 'side population' (SP).

Methods and results: The Hoechst efflux assay was used to isolate and characterize the SP from murine D121 lung carcinoma cells. Here, we demonstrated that D121-SP cells contain cancer stem cell characteristics, that is, upregulation of the transcription factors SOX2 and Oct 4 in D121-SP cells. In addition, the migration of D121-SP was decreased, and apoptosis of D121-SP was upregulated following knocking down of SOX2 in D121 cells. Importantly, downregulation of SOX2 in D121 cells markedly suppressed their metastatic potential in syngeneic mice.

Conclusions: These results suggest that the SP is an enriched source of lung tumour cells with stem cell properties and that SOX2 has an important role in maintaining stem cell properties and functions that may be a potential target for effective lung cancer therapy.

Show MeSH
Related in: MedlinePlus