Oct-4 Expression Maintained Cancer Stem-Like Properties in Lung Cancer-Derived CD133-Positive Cells

Abstract

CD133 (prominin-1), a 5-transmembrane glycoprotein, has recently been considered to be an important marker that represents the subset population of cancer stem-like cells. Herein we report the isolation of CD133-positive cells (LC-CD133+) and CD133-negative cells (LC-CD133−) from tissue samples of ten patients with non-small cell lung cancer (LC) and five LC cell lines. LC-CD133+ displayed higher Oct-4 expressions with the ability to self-renew and may represent a reservoir with proliferative potential for generating lung cancer cells. Furthermore, LC-CD133+, unlike LC-CD133−, highly co-expressed the multiple drug-resistant marker ABCG2 and showed significant resistance to chemotherapy agents (i.e., cisplatin, etoposide, doxorubicin, and paclitaxel) and radiotherapy. The treatment of Oct-4 siRNA with lentiviral vector can specifically block the capability of LC-CD133+ to form spheres and can further facilitate LC-CD133+ to differentiate into LC-CD133−. In addition, knock-down of Oct-4 expression in LC-CD133+ can significantly inhibit the abilities of tumor invasion and colony formation, and increase apoptotic activities of caspase 3 and poly (ADP-ribose) polymerase (PARP). Finally, in vitro and in vivo studies further confirm that the treatment effect of chemoradiotherapy for LC-CD133+ can be improved by the treatment of Oct-4 siRNA. In conclusion, we demonstrated that Oct-4 expression plays a crucial role in maintaining the self-renewing, cancer stem-like, and chemoradioresistant properties of LC-CD133+. Future research is warranted regarding the up-regulated expression of Oct-4 in LC-CD133+ and malignant lung cancer.

Cucurbitacin I inhibits tumorigenic ability and enhances radiochemosensitivity in nonsmall cell lung cancer‐derived CD133‐positive cells

“…12 In our previous study, we demonstrated that nonsmall cell lung cancer (NSCLC)-derived CD133-positive cells displayed higher octamer-binding transcription factor 4 (Oct-4) expression and possessed the ability to self-renew, potentially representing a reservoir of proliferative potential to generate lung cancer cells. 13 Consistent with our findings, Bertolini et al also provided evidence that CD133-positive lung tumor cells possessed stemness features and a higher tumorigenic potential than CD133-negative cells in severe combined immunodeficient (SCID) mice. 14 A growing body of evidence indicates the tumor initiation ability and chemoradioresistance of CD133-positive cells in lung CSCs.…”

“…14,28 Our previous results demonstrated that CD133-positive cells isolated from patients with NSCLC exhibit greater chemoradioresistance compared with NSCLC cells of the CD133-negative lineage. 13 To further explore other possible characteristics of CSCs in CD133-positive cells from patients with lung cancer, we isolated CD133-positive cells (Fig. 1A) in tissue samples from 7 patients with NSCLC using the magnetic bead method ( Table 1).…”

Oct-4+/Tenascin C+ neuroblastoma cells serve as progenitors of tumor-derived endothelial cells

“…Most Oct-4 + cells expressed the catalytic subunit of human telomerase (hTERT) [43] (Supplementary information, Figure S1, 1-3) and the cancer stem cell-related markers CD133 [15] (Supplementary information, Figure S1, 5-7), CD24 [44] (Figure 2B, 13-15), CD271 (nerve growth factor receptor p75) [45], as well as βIII tubulin [46], c-kit and nestin [47,48] (Figure 2A). hTERT, CD133, CD24, nestin and CD271 were expressed in different proportions also by Oct-4 − tumor cells (81% ± 4%, 85% ± 2%, 71% ± 4%, 33% ± 2% and 66% ± 5%, respectively, Figure 2A).…”

“…The Octamer-binding transcription factor 4 (Oct-4), together with SOX-2 and NANOG, maintains self-renewal and blocks cell differentiation in embryonic stem cells [12][13][14] and is expressed by some cancer stem cells [15][16][17][18][19][20]. Among these factors, Oct-4 and SOX-2 appear to be indispensable for stemness maintenance [21].…”

Anti-CSC Effects in Human Esophageal Squamous Cell Carcinomas and Eca109/9706 Cells Induced by Nanoliposomal Quercetin Alone or Combined with CD 133 Antiserum

“…Based on down-regulated ROS stress and cell cycle progression in NIH3T3 cells, E-cancer cells, etc., and facilitating differentiation and apoptosis induced by quercetin in our previous experiments (Gong et al, 2009;Zhang et al, 2007), we found that the natural flavonoid quercetin could persist cell ROS in certain normal level, not only to down-regulate ROS to cells with higher ROS level, but also to up-regulate ROS to cells with lower ROS level. There are some anti-CSC studies in breast, leukemia and glioma tumors induced by green tea polyphenol, curcumin, resveratrol and other polyphenols (Chen et al, 2008;Charpentier et al, 2014). However, the information about quercetin anti-CSC effects in human esophageal stratified squamoous epiththelial cancer has been limited.…”