Table 2.
Summary of current studies of cancer cell reprogramming
| Method | Type of cancer | Malignant‐related phenotype | Characterization | Ref. |
|---|---|---|---|---|
| Nuclear transfer | Medulloblastoma (primary culture, mouse, Ptc1 heterozygous) | Suppressed proliferation, restore normal differentiation, normal proliferation in cultured blastocyst | Cloned blastocyst can support postimplantation development, as the embryo appeared normal and showed extensive differentiation, although not viable after E8.5 | (83) |
| Nuclear transfer (two‐step cloning) | Melanoma RAS+/Ink4a/Arf−/− | NT ES‐cell chimeric mice developed various types of tumors with shorter latency and higher penetrance compared with the donor mouse model | NT ES cells could form teratoma and generate chimera. Injection into tetraploid blastocyst resulted in a normal embryo viable until E9.5 | (84) |
| Nuclear transfer | EC | Dependent on donor ECs, one NT ES cell chimera suffered from head and neck EC and was inviable, and the other resulting NT ES cells showed a broad differentiation potential into teratomas and broad contribution to normal‐appearing mid‐gestation embryos | Nuclei from EC can direct preimplantation development, resulting in normal appearing blastocyst, higher efficiency of producing an ES cell line compared with the differentiated cells, although the degree of differentiation depends on the cell line character | (85) |
| Embryonic microenvironment | Metastatic melanoma, breast cancer | Reduced invasion, tumor growth, increased apoptosis Downregulated Nodal signaling through Lefty activation | n.d. | (86) |
| microRNA (miR‐302a, b, c, d) | Melanoma (Colo), prostate cancer cell line (PC3) | Reduced migration ability, reduced expression of cell cycle‐related genes (CCND1, CCND2, CDK2), and DNA methylation facilitator, MeCP2 MECP1‐p66, and some melanoma oncogenes | Expression of pluripotency markers Nanog, Oct4, Sox2, SSEA3, SSEA4 Demethylation of Oct4 Teratoma (+) | (9) |
| Defined transcription factor (OKM) | Melanoma (R545) | Chimeras were tumor‐free at 5 months of age | Teratoma (+), chimera (+), ES cell marker expression, demethylation of Nanog and Oct4 | (87) |
| Defined transcription factor (OSKM) | Gastrointestinal cancer (colon, liver, pancreatic cancer) DLD‐1 completely characterized | Differentiated iPC (post‐iPC) showed sensitivity to chemotherapy, reduced invasion, and reduced tumorigenicity, showed higher expression of p16 and p53 as compared to the parental cell | Expression of pluripotency marker, demethylation of Nanog, in vitro differentiation into adipocyte, epithelial, mesenchymal, and neural lineage, teratoma (−) | (10) |
| Defined transcription factor (OSKM) | KBM7 cells derived from blast crisis stage chronic myeloid leukemia (CML) | Completely resistant to imatinib, loss of BCR‐ABL‐dependent signaling | ES cell marker expression (+), demethylation of Oct4 and Nanog, teratoma (+) | (88) |
| Defined transcription factor (OSLN) | A549 lung cancer | Increased tumorigenic properties when transplanted into a NOD/SCID mouse, more aggressive and invasive, teratoma (−) | Demethylation of Oct4 promoter expressed endogenous Nanog and Oct4 although lower than HES cell ALP(+), teratoma (−) Reprogramming efficiency was higher compared with normal primary lung fibroblast | (89) |
| Oocyte extract | Breast cancer (MCF7 and HCC1945 cell lines) | Re‐expression of tumor suppressor genes RARB, CST6, CCND2, CDKN2A through demethylation and remodeling of histone marks to a more euchromatic state No changes in DNA methylation at pluripotency gene promoters Oct4/Nanog Reduced colony formation | n.d. | (90) |
ALP, alkaline phosphatase (staining); EC, embryonal carcinoma; HES, human embryonic stem; iPC, induced pluripotent stem (iPS)‐like cancer cells; K, Klf4; L, Lin28; M, c‐Myc; N, Nanog; n.d., not determined; NT ES, nuclear transfer‐generated embryonic stem cells; O, Oct3/4; Ref., reference; S, Sox2.