Heterogeneity of Osteosarcoma Cell Lines Led to Variable Responses in Reprogramming

Abstract

Four osteosarcoma cell lines, Saos-2, MG-63, G-292 and U-2 OS, were reprogrammed to pluripotent state using Yamanaka factors retroviral transduction method. Embryonic stem cell (ESC)-like clusters started to appear between 15 to 20 days post transduction. Morphology of the colonies resembled that of ESC colonies with defined border and tightly-packed cells. The reprogrammed sarcomas expressed alkaline phosphatase and pluripotency markers, OCT4, SSEA4, TRA-1-60 and TRA-1-81, as in ESC up to Passage 15. All reprogrammed sarcomas could form embryoid body-like spheres when cultured in suspension in a low attachment dish for up to 10 days. Further testing on the directed differentiation capacity of the reprogrammed sarcomas showed all four reprogrammed sarcoma lines could differentiate into adipocytes while reprogrammed Saos-2-REP, MG-63-REP and G-292-REP could differentiate into osteocytes. Among the 4 osteosarcoma cell lines, U-2 OS reported the highest transduction efficiency but recorded the lowest reprogramming stability under long term culture. Thus, there may be intrinsic differences governing the variable responses of osteosarcoma cell lines towards reprogramming and long term culture effect of the reprogrammed cells. This is a first report to associate intrinsic factors in different osteosarcoma cell lines with variable reprogramming responses and effects on the reprogrammed cells after prolonged culture.

Reprogramming cancer cells: A novel approach for cancer therapy or a tool for disease-modeling?

“…Apart from the studies described in sections b and c above, several groups have reprogrammed cancer cells however did not analyze the tumorgineic potential of the resulting cancer iPS cells [60,61,65,66]. They mainly determined whether these cells carry characteristics of pluripotent stem cells and whether pluripotency can be maintained in these reprogrammed cells.…”

“…Such clonal heterogeneity indicates that many human tumors are histopathologically and genetically diverse [80]. Due to this heterogeneous population of cells, it is expected to see that cellular reprogramming can favor specific clones resulting in reduced or increased tumorigenicity [65]. This also points out the importance of using both cancer cell lines and patient-derived tumor cells in cancer cell reprogramming studies in order to better understand the effect of tumor heterogeneity.…”

“…Activation of transcription factors and modification of chromatin regulators may result in the remodeling of epigenetic status and refueling of tumorigenicity in these reprogrammed cancer cells. However, until now, studies that focused on cancer cell reprogramming [58][59][60][61][62][63][64][65][66][67] are contradictory; some studies reported increased tumor progression whereas others showed cellular reprogramming has a treatment potential for cancer:…”

Advances and Challenges on Cancer Cells Reprogramming Using Induced Pluripotent Stem Cells Technologies

“…Reprogrammed sarcoma cells showed capacity to differentiate into adipocytes and osteocytes. They showed variable responses of reprogramming in respect of efficiency and long term culture effect 46.…”

Lectin from green speckled lentil seeds (Lens culinaris) triggered apoptosis in nasopharyngeal carcinoma cell lines

“…The sequence and structure of LcLs have been elucidated [ 9 ], and they bind to glucose, mannose, and some glucose- and mannose-containing sugars, as well as to α- d -mannopyranosyl and α- d -glucopyranosyl residues of glycoproteins and glycolipids [ 10 ]. LcLs can bind to specific carbohydrate groups of glycoproteins on cell surfaces, thus allowing studies on differences in the levels of glycoproteins in different cell types [ 11 , 12 ]. They are also used in affinity chromatography for detection of glucose- and mannose-containing biomarkers, e.g., LcLs can bind to α-fetoprotein in the blood for diagnosis of hepatocellular carcinoma [ 13 , 14 ].…”