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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

Determination of clone formation efficiency of osteosarcoma SP cells. (A) The SP cells generate sarcospheres rapidly and significantly higher than non-SP cells. Values are expressed as the mean ± standard deviation. **P<0.01 for non-SP vs. SP. (B) Representative phase contrast images showing that SP cell-derived sarcospheres are bigger in size than those of non-SP cells. (C) Fluorescence microscopic images showing that SP cell-derived sarcospheres are CD133- and Oct3/4A-positive (magnification, ×100). SP, side population; Oct, octamer-binding transcription factor.
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f4-mmr-12-04-5665: Determination of clone formation efficiency of osteosarcoma SP cells. (A) The SP cells generate sarcospheres rapidly and significantly higher than non-SP cells. Values are expressed as the mean ± standard deviation. **P<0.01 for non-SP vs. SP. (B) Representative phase contrast images showing that SP cell-derived sarcospheres are bigger in size than those of non-SP cells. (C) Fluorescence microscopic images showing that SP cell-derived sarcospheres are CD133- and Oct3/4A-positive (magnification, ×100). SP, side population; Oct, octamer-binding transcription factor.

Mentions: One of the most important characteristic features of SP cells is their ability to self-renew. It was reported that side population cells from several solid tumors have a high proliferation rate and are able to efficiently propagate the tumor population. In order to assess the self-renewal capacity of SP cells, a clonogenic formation efficiency test was performed. After 6 days of culturing, it was observed that the purified SP cells were able to generate significantly more clusters of tumor spheres (sarcospheres) than non-SP cells (Fig. 4A). Furthermore, the sarcospheres generated by SP cells were bigger in size when compared to the non-SP spheres (Fig. 4B). Of note, these sarcospheres were positive for stem cell surface markers, including CD133 and Oct-3/4A (Fig. 3C). Hence, these results clearly suggested that elevated expression of stem cell proteins in SP cells has a major role in tumor initiation and re-population.


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)

Determination of clone formation efficiency of osteosarcoma SP cells. (A) The SP cells generate sarcospheres rapidly and significantly higher than non-SP cells. Values are expressed as the mean ± standard deviation. **P<0.01 for non-SP vs. SP. (B) Representative phase contrast images showing that SP cell-derived sarcospheres are bigger in size than those of non-SP cells. (C) Fluorescence microscopic images showing that SP cell-derived sarcospheres are CD133- and Oct3/4A-positive (magnification, ×100). SP, side population; Oct, octamer-binding transcription factor.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4-mmr-12-04-5665: Determination of clone formation efficiency of osteosarcoma SP cells. (A) The SP cells generate sarcospheres rapidly and significantly higher than non-SP cells. Values are expressed as the mean ± standard deviation. **P<0.01 for non-SP vs. SP. (B) Representative phase contrast images showing that SP cell-derived sarcospheres are bigger in size than those of non-SP cells. (C) Fluorescence microscopic images showing that SP cell-derived sarcospheres are CD133- and Oct3/4A-positive (magnification, ×100). SP, side population; Oct, octamer-binding transcription factor.
Mentions: One of the most important characteristic features of SP cells is their ability to self-renew. It was reported that side population cells from several solid tumors have a high proliferation rate and are able to efficiently propagate the tumor population. In order to assess the self-renewal capacity of SP cells, a clonogenic formation efficiency test was performed. After 6 days of culturing, it was observed that the purified SP cells were able to generate significantly more clusters of tumor spheres (sarcospheres) than non-SP cells (Fig. 4A). Furthermore, the sarcospheres generated by SP cells were bigger in size when compared to the non-SP spheres (Fig. 4B). Of note, these sarcospheres were positive for stem cell surface markers, including CD133 and Oct-3/4A (Fig. 3C). Hence, these results clearly suggested that elevated expression of stem cell proteins in SP cells has a major role in tumor initiation and re-population.

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