Chick Embryo Extract Demethylates Tumor Suppressor Genes in Osteosarcoma Cells

Abstract

Background Epigenetics is the study of changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence. It is widely accepted that cancer has genetic and epigenetic origins. The idea of epigenetic reprogramming of cancer cells by an embryonic microenvironment possesses potential interest from the prospect of both basic science and potential therapeutic strategies. Chick embryo extract (CEE) has been used for the successful expansion of many specific stem cells and has demonstrated the ability to facilitate DNA demethylation.Questions/purposes The current study was conducted to compare the status of DNA methylation in highly metastatic and less metastatic osteosarcoma cells and to investigate whether CEE may affect the epigenetic regulation of tumor suppressor genes and thus change the metastatic phenotypes of highly metastatic osteosarcoma cells. Methods K7M2 murine OS cells were treated with CEE to determine its potential effect on DNA methylation, cell apoptosis, and invasion capacity. Results Our current results suggest that the methylation status of tumor suppressor genes (p16, p53, and E-cadherin) is significantly greater in highly metastatic mouse ostoesarcoma K7M2 cells in comparison with less metastatic mouse osteosarcoma K12 cells. CEE treatment of K7M2 cells caused demethylation of p16, p53, and E-cadherin genes, upregulated their expression, and resulted in the reversion of metastatic phenotypes in highly metastatic osteosarcoma cells. Conclusions CEE may promote the reversion of metastatic phenotypes of osteosarcoma cells and can be a helpful tool to study osteosarcoma tumor reversion by epigenetic reprogramming. Clinical Relevance Demethylation of tumor suppressor genes in osteosarcoma may represent a novel strategy to diminish the metastatic potential of this neoplasm. Further studies, both in vitro and in vivo, are warranted to evaluate the clinical feasibility of this approach as an adjuvant to current therapy.

Osteosarcomagenesis: Biology, Development, Metastasis, and Mechanisms of Pain

“…Alterations in the TP53 gene have signiicant efects on the downstream signaling targets, many of which are normally involved in cell cycle control and apoptosis. Gene rearrangements, point mutations, epigenetic modiication [28,29], and/or allelic loss can presumably lead to inactivation of normal TP53 function, and these aberrations have been associated with the development of osteosarcoma. In a recent study that characterized the genomic landscape of osteosarcoma via whole genome sequencing (WGS), the majority of TP53 inactivation in osteosarcoma was found to be due to translocations [30].…”

Osteogenic Sarcoma: A 21st Century Review

“…Demethylation of the promoter regions of TSSC3, a proapoptotic gene, resulted in overexpression of the gene thereby suppressing the growth of BOS cell lines (27). Mu et al reported that demethylation of tumor-suppressor genes in BOS may reduce the metastatic capability of the tumor (28,29). Some microRNAs (miRNAs) are also suggested to be markers of prognosis (30).…”

The chick embryo as an expanding experimental model for cancer and cardiovascular research

“…Most importantly, the avian CAM successfully supports most cancer cell characteristics including growth, invasion, angiogenesis, and remodeling of the microenvironment. This makes the model exceptionally useful for investigating the molecular pathways of oncogenesis (Zijlstra et al, ; Bobek et al, ; Fergelot et al, ; Liu et al, ; Mu et al, ).…”

“…This fundamentally changed our understanding of the genesis and growth of cancer and reinforced the applicability of chicken research to human health. Since the early studies by Rous, chicks have been used in a wide array of oncology studies to evaluate the causes of tumor initiation and cancer growth, as well as the mechanisms of tumor cell invasion, metastasis, and angiogenesis (Stern, ; Zijlstra et al, ; Liu et al, ; Mu et al, ).…”