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

Dong-Xiu Sun; Guang-Jun Liao; Ke-Gui Liu; Han Jian

doi:10.3892/mmr.2015.4218

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

Mol Med Rep. 2015 Oct;12(4):5665-70. doi: 10.3892/mmr.2015.4218. Epub 2015 Aug 12.

Authors

Dong-Xiu Sun¹, Guang-Jun Liao², Ke-Gui Liu³, Han Jian²

Affiliations

¹ Department of Operating Room, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China.
² Department of Orthopaedic Surgery, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China.
³ The Joint Department of Orthopaedics, 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.

MeSH terms

AC133 Antigen
ATP-Binding Cassette Transporters / genetics
ATP-Binding Cassette Transporters / metabolism
Adult
Antigens, CD / genetics*
Antigens, CD / metabolism
Antigens, Neoplasm / genetics*
Antigens, Neoplasm / metabolism
Antineoplastic Agents / pharmacology
Bone Neoplasms / drug therapy
Bone Neoplasms / genetics
Bone Neoplasms / pathology
Bone Neoplasms / surgery
Cell Proliferation / drug effects
Drug Resistance, Neoplasm / genetics*
Female
Gene Expression Regulation, Neoplastic*
Glycoproteins / genetics
Glycoproteins / metabolism
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism
Humans
Male
Nanog Homeobox Protein
Neoplasm Invasiveness
Neoplastic Stem Cells / drug effects
Neoplastic Stem Cells / metabolism*
Neoplastic Stem Cells / pathology
Nestin / genetics
Nestin / metabolism
Octamer Transcription Factor-3 / genetics
Octamer Transcription Factor-3 / metabolism
Osteoblasts / drug effects
Osteoblasts / metabolism*
Osteoblasts / pathology
Osteosarcoma / drug therapy
Osteosarcoma / genetics
Osteosarcoma / pathology
Osteosarcoma / surgery
Peptides / genetics
Peptides / metabolism
Primary Cell Culture
Side-Population Cells / drug effects
Side-Population Cells / metabolism*
Side-Population Cells / pathology
Signal Transduction

Substances

AC133 Antigen
ATP-Binding Cassette Transporters
Antigens, CD
Antigens, Neoplasm
Antineoplastic Agents
CD248 protein, human
Glycoproteins
Homeodomain Proteins
NANOG protein, human
NES protein, human
Nanog Homeobox Protein
Nestin
Octamer Transcription Factor-3
POU5F1 protein, human
PROM1 protein, human
Peptides