Title
Expression of an Exogenous Human Oct-4 Promoter Identifies Tumor-Initiating Cells in Osteosarcoma
Abbreviated Journal Title
Cancer Res.
Keywords
CANCER STEM-CELLS; PRIMARY BIOASSAY; BREAST-CANCER; SOMATIC-CELLS; HYBRID-CELLS; IN-VITRO; PLURIPOTENCY; BIOLOGY; CLONES; CYCLE; Oncology
Abstract
We explored the nature of the tumor-initiating cell in osteosarcoma, a bone malignancy that predominately occurs in children. Previously, we observed expression of Oct-4, an embryonal transcriptional regulator, in osteosarcoma cell cultures and tissues. To examine the relationship between Oct-4 and tumorigenesis, cells from an osteosarcoma biopsy (OS521) were stably transfected with a plasmid containing the human Oct-4 promoter driving a green fluorescent protein (GFP) reporter to generate the transgenic line OS521Oct-4p. In culture, only similar to 24% of the OS521Oct-4p cells were capable of activating the transgenic Oct-4 promoter; yet, xenograft tumors generated in NOD/SCID mice contained similar to 67% GFP(+) cells, which selectively expressed the mesenchymal stem cell-associated surface antigens CD105 and ICAM-1. Comparison of the tumor-forming capacity of GFP-enriched and GFP-depleted cell fractions revealed that the GFP-enriched fractions were at least 100-fold more tumorigenic, capable of forming tumors at doses of <300 cells, and formed metastases in the lung. Clonal populations derived from a single Oct-4/GFP(+) cell were capable of forming tumors heterogeneous for Oct-4/GFP expression. These data are consistent with the cancer stem cell model of tumorigenesis in osteosarcoma and implicate a functional link between the capacity to activate an exogenous Oct-4 promoter and tumor formation. This osteosarcoma tumor-initiating cell appears highly prolific and constitutes a majority of the cell population in a primary xenograft tumor, which may provide a biological basis for the particular virulence of this type of cancer. [Cancer Res 2009;69(14):5648-55]
Journal Title
Cancer Research
Volume
69
Issue/Number
14
Publication Date
1-1-2009
Document Type
Article
Language
English
First Page
5648
Last Page
5655
WOS Identifier
ISSN
0008-5472
Recommended Citation
"Expression of an Exogenous Human Oct-4 Promoter Identifies Tumor-Initiating Cells in Osteosarcoma" (2009). Faculty Bibliography 2000s. 1788.
https://stars.library.ucf.edu/facultybib2000/1788