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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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Related in: MedlinePlus

Upregulation of stem cell-associated transcription factors SOX2 and Oct 4 on D121-SP cells. (A) The expression of SOX2 and Oct 4, but not Wnt-1 and 10 were found to be upregulated in the SP cells derived from D121 lung cancer cells as detected by RT–PCR and immunoflorence histology staining (B).
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fig3: Upregulation of stem cell-associated transcription factors SOX2 and Oct 4 on D121-SP cells. (A) The expression of SOX2 and Oct 4, but not Wnt-1 and 10 were found to be upregulated in the SP cells derived from D121 lung cancer cells as detected by RT–PCR and immunoflorence histology staining (B).

Mentions: To determine which key transcription factors are involved in maintaining stem cell characteristics we further analysed SP from D121 cells for the expression of these important stem cell-associated molecules. To this end, RT–PCR was performed to determine expressions of SOX2, Oct 4, Notch-1 and Wnt-1, 2 and Wnt-10a either in sorted SP or non-SP D121 cells. The results indicated that expressions of SOX2 and Oct 4, but not those of Wnt-1, 2 and10a, were upregulated in SP cells isolated from D121 tumour cells when compared with those of non-SP cells (Figure 3A). To further confirm these results, immunohistochemical fluorescence staining was used with either anti-SOX2 or Oct 4 antibodies (Figure 3B). Our findings clearly indicated a markedly higher expression of SOX2 and Oct 4 in D121-SP cells than that observed in non-SP cells. These data suggest that the transcription factor SOX2 together with its partner gene might have an important role in the maintenance of tumour stem cell characteristics.


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-associated transcription factors SOX2 and Oct 4 on D121-SP cells. (A) The expression of SOX2 and Oct 4, but not Wnt-1 and 10 were found to be upregulated in the SP cells derived from D121 lung cancer cells as detected by RT–PCR and immunoflorence histology staining (B).
© Copyright Policy
Related In: Results  -  Collection

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

fig3: Upregulation of stem cell-associated transcription factors SOX2 and Oct 4 on D121-SP cells. (A) The expression of SOX2 and Oct 4, but not Wnt-1 and 10 were found to be upregulated in the SP cells derived from D121 lung cancer cells as detected by RT–PCR and immunoflorence histology staining (B).
Mentions: To determine which key transcription factors are involved in maintaining stem cell characteristics we further analysed SP from D121 cells for the expression of these important stem cell-associated molecules. To this end, RT–PCR was performed to determine expressions of SOX2, Oct 4, Notch-1 and Wnt-1, 2 and Wnt-10a either in sorted SP or non-SP D121 cells. The results indicated that expressions of SOX2 and Oct 4, but not those of Wnt-1, 2 and10a, were upregulated in SP cells isolated from D121 tumour cells when compared with those of non-SP cells (Figure 3A). To further confirm these results, immunohistochemical fluorescence staining was used with either anti-SOX2 or Oct 4 antibodies (Figure 3B). Our findings clearly indicated a markedly higher expression of SOX2 and Oct 4 in D121-SP cells than that observed in non-SP cells. These data suggest that the transcription factor SOX2 together with its partner gene might have an important role in the maintenance of tumour stem cell characteristics.

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