Abstract
Osteosarcoma (OS) cell lines are widely used in understanding the biological functions of cancer, identification and validation of therapeutic targets, as well as in vitro or in vivo preclinical drug screening. Here we report there is a frequent loss-of-function of polycomb repressive complex 2 (PRC2) in OS cell lines but it is rare in tumor samples based on genomic sequencing data, western blotting and immunohistochemistry analysis of H3K27me3. U2OS and 143B cell lines have a complete loss of function of PRC2 and several others have partial loss. In OS tumor tissues, only 1 out of 14 has low expression of H3K27me3. Kaplan-Meier analysis indicates that high EZH2, the component of PRC2, is associated with poor metastasis-free survival. Our observations are to raise the alarm that particular caution should be taken when using OS cell line models to study the disease, functional genomics, therapeutic target validation, drug screening, and epigenetic studies. Nevertheless, these cell lines will become useful biological tools to dissect the functions of PRC2.
Highlights
Osteosarcoma (OS) is the most prevalent primary bone tumor and has a high propensity to metastasize
It is well known that genetic features of cell lines may not represent those of primary tumor cells in vivo, established OS cell lines are widely used in understanding the biological functions of cancer cells, identification and validation of therapeutic targets, as well as in vitro or in vivo preclinical drug screening
It is likely that the genetic/epigenetic loss-of-function of polycomb repressive complex 2 (PRC2) in OS cells is due to selection under culture stress or intrinsic genetic instability, there is a third possibility that these cells were derived from rare clones that expanded when the cell lines were established using bulk tumor cells, especially for samples taken from relapsed, metastasized, or refractory disease
Summary
Osteosarcoma (OS) is the most prevalent primary bone tumor and has a high propensity to metastasize. Cancer biologists realized that gene expression and phenotype, including drug response, vary greatly due to culture conditions and passage numbers. These differences are one explanation for variations in biological processes in the in vitro and in vivo settings, which causes difficulties for data reproducibility. We report a frequent loss-of-function of polycomb repressive complex 2 (PRC2) in OS cell lines. This observation appears to be a rare event in primary tumor samples, and may be a unique feature of some OS cell lines. Either gain or loss of function of PRC2 may lead to therapeutic resistance under different cellular context [12,13,14,15,16]
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