The molecular portrait of in vitro growth by meta-analysis of gene-expression profiles

Cell lines as model systems of tumors and tissues are essential in molecular biology, although they only approximate the properties of in vivo cells in tissues. Cell lines have been selected under in vitro conditions for a long period of time, affecting many specific cellular pathways and processes.

To identify the transcriptional changes caused by long term in vitro selection, we performed a gene-expression meta-analysis and compared 60 tumor cell lines (of nine tissue origins) to 135 human tissue and 176 tumor tissue samples. Using significance analysis of microarrays we demonstrated that cell lines showed statistically significant differential expression of approximately 30% of the approximately 7,000 genes investigated compared to the tissues. Most of the differences were associated with the higher proliferation rate and the disrupted tissue organization in vitro. Thus, genes involved in cell-cycle progression, macromolecule processing and turnover, and energy metabolism were upregulated in cell lines, whereas cell adhesion molecules and membrane signaling proteins were downregulated.

Detailed molecular understanding of how cells adapt to the in vitro environment is important, as it will both increase our understanding of tissue organization and result in a refined molecular portrait of proliferation. It will further indicate when to use immortalized cell lines, or when it is necessary to instead use three-dimensional cultures, primary cell cultures or tissue biopsies.