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Endosialin‑expressing bone sarcoma stem‑like cells are highly tumor‑initiating and invasive.

Sun DX, Liao GJ, Liu KG, Jian H - Mol Med Rep (2015)

Bottom Line: The present study demonstrated that primary human osteosarcoma samples contained a SP of about 3.9% which overexpressed ABC transporters, including ABCA1, ABCB1, ABCB2 and ABCG2, which are associated with drug resistance and may have contributed to multi‑drug resistance of SP cells.Furthermore, these SP cells displayed increased expression of endosialin (CD248) and other stem cell surface proteins, including CD133, octamer‑binding transcription factor 3/4A, Nanog and Nestin, which are ultimately responsible for high self‑renewal and deregulated cell proliferation.In addition, it was shown that endosialin‑overexpressing SP cells were able to regenerate the tumor population and had a high invasive potential.

View Article: PubMed Central - PubMed

Affiliation: Department of Operating Room, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China.

ABSTRACT
It has been reported that the presence of a small group of cancer stem‑like 'side population (SP)' cells is responsible for therapy failure and tumor recurrence. The present study demonstrated that primary human osteosarcoma samples contained a SP of about 3.9% which overexpressed ABC transporters, including ABCA1, ABCB1, ABCB2 and ABCG2, which are associated with drug resistance and may have contributed to multi‑drug resistance of SP cells. Furthermore, these SP cells displayed increased expression of endosialin (CD248) and other stem cell surface proteins, including CD133, octamer‑binding transcription factor 3/4A, Nanog and Nestin, which are ultimately responsible for high self‑renewal and deregulated cell proliferation. In addition, it was shown that endosialin‑overexpressing SP cells were able to regenerate the tumor population and had a high invasive potential. Therefore, the present study suggested that osteosarcoma SP cells were cancer stem cells, as they displayed stem‑like properties; furthermore, endosialin may be a potential target to prevent osteosarcoma recurrence following chemotherapy.

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Related in: MedlinePlus

Identification of SP cells from human osteosarcoma. Live cells were selected against propidium iodide staining. (A) Dot plot of FACS analysis showing the presence of 3.9% of SP cells (gated population). (B) After treatment with verapamil (adenosine triphosphate binding cassette transporter inhibitor) treatment, the SP cell population was diminished to 0.7%. (C) Results of FACS analysis quantified from three independent experiments. **P<0.01 for non-SP vs. SP. SP, side population; FACS, fluorescence-associated cell sorting.
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f1-mmr-12-04-5665: Identification of SP cells from human osteosarcoma. Live cells were selected against propidium iodide staining. (A) Dot plot of FACS analysis showing the presence of 3.9% of SP cells (gated population). (B) After treatment with verapamil (adenosine triphosphate binding cassette transporter inhibitor) treatment, the SP cell population was diminished to 0.7%. (C) Results of FACS analysis quantified from three independent experiments. **P<0.01 for non-SP vs. SP. SP, side population; FACS, fluorescence-associated cell sorting.

Mentions: Human osteosarcoma samples obtained from the patients were analyzed for the presence of SP cells by the FACS-based Hoechst 33342 dye exclusion method. In the FACS dot plot, a 3.9%-population of SP cells was gated in the lower left quadrant (Fig. 1A). After treatment with Verapamil, an inhibitor of ABC transporters, the population of SP cells was diminished to 0.7% (Fig. 1B and C). Therefore, these results confirmed the role of the ABC transporter ABCG2 in treatment resistance-associated drug expulsion by SP cells.


Endosialin‑expressing bone sarcoma stem‑like cells are highly tumor‑initiating and invasive.

Sun DX, Liao GJ, Liu KG, Jian H - Mol Med Rep (2015)

Identification of SP cells from human osteosarcoma. Live cells were selected against propidium iodide staining. (A) Dot plot of FACS analysis showing the presence of 3.9% of SP cells (gated population). (B) After treatment with verapamil (adenosine triphosphate binding cassette transporter inhibitor) treatment, the SP cell population was diminished to 0.7%. (C) Results of FACS analysis quantified from three independent experiments. **P<0.01 for non-SP vs. SP. SP, side population; FACS, fluorescence-associated cell sorting.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581793&req=5

f1-mmr-12-04-5665: Identification of SP cells from human osteosarcoma. Live cells were selected against propidium iodide staining. (A) Dot plot of FACS analysis showing the presence of 3.9% of SP cells (gated population). (B) After treatment with verapamil (adenosine triphosphate binding cassette transporter inhibitor) treatment, the SP cell population was diminished to 0.7%. (C) Results of FACS analysis quantified from three independent experiments. **P<0.01 for non-SP vs. SP. SP, side population; FACS, fluorescence-associated cell sorting.
Mentions: Human osteosarcoma samples obtained from the patients were analyzed for the presence of SP cells by the FACS-based Hoechst 33342 dye exclusion method. In the FACS dot plot, a 3.9%-population of SP cells was gated in the lower left quadrant (Fig. 1A). After treatment with Verapamil, an inhibitor of ABC transporters, the population of SP cells was diminished to 0.7% (Fig. 1B and C). Therefore, these results confirmed the role of the ABC transporter ABCG2 in treatment resistance-associated drug expulsion by SP cells.

Bottom Line: The present study demonstrated that primary human osteosarcoma samples contained a SP of about 3.9% which overexpressed ABC transporters, including ABCA1, ABCB1, ABCB2 and ABCG2, which are associated with drug resistance and may have contributed to multi‑drug resistance of SP cells.Furthermore, these SP cells displayed increased expression of endosialin (CD248) and other stem cell surface proteins, including CD133, octamer‑binding transcription factor 3/4A, Nanog and Nestin, which are ultimately responsible for high self‑renewal and deregulated cell proliferation.In addition, it was shown that endosialin‑overexpressing SP cells were able to regenerate the tumor population and had a high invasive potential.

View Article: PubMed Central - PubMed

Affiliation: Department of Operating Room, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China.

ABSTRACT
It has been reported that the presence of a small group of cancer stem‑like 'side population (SP)' cells is responsible for therapy failure and tumor recurrence. The present study demonstrated that primary human osteosarcoma samples contained a SP of about 3.9% which overexpressed ABC transporters, including ABCA1, ABCB1, ABCB2 and ABCG2, which are associated with drug resistance and may have contributed to multi‑drug resistance of SP cells. Furthermore, these SP cells displayed increased expression of endosialin (CD248) and other stem cell surface proteins, including CD133, octamer‑binding transcription factor 3/4A, Nanog and Nestin, which are ultimately responsible for high self‑renewal and deregulated cell proliferation. In addition, it was shown that endosialin‑overexpressing SP cells were able to regenerate the tumor population and had a high invasive potential. Therefore, the present study suggested that osteosarcoma SP cells were cancer stem cells, as they displayed stem‑like properties; furthermore, endosialin may be a potential target to prevent osteosarcoma recurrence following chemotherapy.

Show MeSH
Related in: MedlinePlus