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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

Drug sensitivity assay. SP cells showed an increased drug resistance and an enhanced survival rate after treatment with doxorubicin, cisplatin or methotrexate. Values are expressed as the mean ± standard deviation of three independent experiments. **P<0.01 for non-SP vs. SP. SP, side population.
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f5-mmr-12-04-5665: Drug sensitivity assay. SP cells showed an increased drug resistance and an enhanced survival rate after treatment with doxorubicin, cisplatin or methotrexate. Values are expressed as the mean ± standard deviation of three independent experiments. **P<0.01 for non-SP vs. SP. SP, side population.

Mentions: SP cells were shown to resist several drugs and thus, to be responsible for treatment failure and tumor relapse. In order to test the drug resistance capacities of SP and non-SP cells, a drug resistance assay was performed. After treatment with the drugs doxorubicin, cisplatin and methotrexate, the survival rate of SP cells was >80%, whereas it was <30% for non-SP cells (Fig. 5A). These results confirmed that SP cells are highly resistant to several chemotherapeutic drugs. Next, the present study investigated the cause for chemoresistance of SP cells. From Fig. 1 it is clear that dye exclusion of SP cells actively involves the upregulation of ABC transporter proteins. Therefore, the present study performed a comprehensive RT-qPCR analysis of SP and non-SP cells to evaluate the transcriptional upregulation of various ABC transporters including ABCA1, ABCB1, ABCA2 and ABCG2. As shown in the graph in Fig. 6A, all of the assessed ABC transporter genes were markedly upregulated in SP cells, indicating that they are responsible for the drug resistance of osteosarcoma by actively pumping chemotherapeutic drugs out of the SP cells. Furthermore, in order to determine the invasion potential of SP cells, a Matrigel invasion assay was performed. The results showed that SP cells have an enhanced invasive capacity compared with that of non-SP cells (Fig. 6B). Hence, these findings suggested that osteosarcoma SP cells display marked drug resistance and have tumor-initiating as well as invasive properties.


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)

Drug sensitivity assay. SP cells showed an increased drug resistance and an enhanced survival rate after treatment with doxorubicin, cisplatin or methotrexate. Values are expressed as the mean ± standard deviation of three independent experiments. **P<0.01 for non-SP vs. SP. SP, side population.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5-mmr-12-04-5665: Drug sensitivity assay. SP cells showed an increased drug resistance and an enhanced survival rate after treatment with doxorubicin, cisplatin or methotrexate. Values are expressed as the mean ± standard deviation of three independent experiments. **P<0.01 for non-SP vs. SP. SP, side population.
Mentions: SP cells were shown to resist several drugs and thus, to be responsible for treatment failure and tumor relapse. In order to test the drug resistance capacities of SP and non-SP cells, a drug resistance assay was performed. After treatment with the drugs doxorubicin, cisplatin and methotrexate, the survival rate of SP cells was >80%, whereas it was <30% for non-SP cells (Fig. 5A). These results confirmed that SP cells are highly resistant to several chemotherapeutic drugs. Next, the present study investigated the cause for chemoresistance of SP cells. From Fig. 1 it is clear that dye exclusion of SP cells actively involves the upregulation of ABC transporter proteins. Therefore, the present study performed a comprehensive RT-qPCR analysis of SP and non-SP cells to evaluate the transcriptional upregulation of various ABC transporters including ABCA1, ABCB1, ABCA2 and ABCG2. As shown in the graph in Fig. 6A, all of the assessed ABC transporter genes were markedly upregulated in SP cells, indicating that they are responsible for the drug resistance of osteosarcoma by actively pumping chemotherapeutic drugs out of the SP cells. Furthermore, in order to determine the invasion potential of SP cells, a Matrigel invasion assay was performed. The results showed that SP cells have an enhanced invasive capacity compared with that of non-SP cells (Fig. 6B). Hence, these findings suggested that osteosarcoma SP cells display marked drug resistance and have tumor-initiating as well as invasive properties.

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