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Profiling of pathway-specific changes in gene expression following growth of human cancer cell lines transplanted
Chad Creighton1, Rork Kuick, David E Misek
1Bioinformatics Program, Human Genetics, and Public Health, University of Michigan, Ann Arbor, MI 48109, USA. ccreight@umich.edu
Background:
Tumor cells cultured in vitro are widely used to investigate the molecular biology of cancers and to evaluate responses to drugs and other agents. The full extent to which gene expression in cancer cells is modulated by extrinsic factors and by the microenvironment in which the cancer cells reside remains to be determined. Two cancer cell lines (A549 lung adenocarcinoma and U118 glioblastoma) were transplanted subcutaneously into immunodeficient mice to form tumors. Global gene-expression profiles of the tumors were determined, based on analysis of expression of human genes, and compared with expression profiles of the cell lines grown in culture.
Results:
A bioinformatics approach associated genes that showed changes in their expression levels with functional classes as defined by either the GO gene annotations or MeSH terms in the literature. The classes of genes expressed at higher levels in cells grown in vitro indicated increased cell division and metabolism, reflecting the more favorable environment for cell proliferation. In contrast, in vivo tumor growth resulted in upregulation of a significant number of genes involved in the extracellular matrix (ECM), cell adhesion, cytokine and metalloendopeptidase activity, and neovascularization. When placed in comparable tissue environments, the U118 cells and the A549 cells expressed different sets of ECM and cell adhesion-related genes, suggesting different mechanisms of extracellular interaction at work in the different cancers.
Conclusions:
Studies of this type allow us to examine the specific contribution of cancer cells to gene expression patterns within an in vivo tumor mixed with non-cancerous tissue.
Insights
Cancer cells grown in vivo show distinct gene expression patterns compared to those cultured in vitro. The tumor microenvironment significantly alters gene activity, impacting cell division, metabolism, and extracellular matrix interactions.
Area of Science:
- Cancer Biology
- Molecular Oncology
- Genomics
Background:
- In vitro tumor cell cultures are standard for cancer research and drug testing.
- The influence of the microenvironment on cancer cell gene expression requires further investigation.
Purpose of the Study:
- To compare gene expression profiles of cancer cell lines grown in vitro versus in vivo within a tumor microenvironment.
- To identify specific gene expression changes induced by the in vivo tumor environment.
Main Methods:
- Two cancer cell lines (A549 lung adenocarcinoma, U118 glioblastoma) were xenografted into immunodeficient mice.
- Global gene expression profiling of human genes was performed on both cultured cells and derived tumors.
- Bioinformatics analysis correlated gene expression changes with functional gene annotations (GO) and MeSH terms.
Main Results:
- In vitro conditions favored genes associated with cell division and metabolism.
- In vivo tumor growth upregulated genes involved in extracellular matrix (ECM) interaction, cell adhesion, cytokine activity, and neovascularization.
- Different cancer cell lines exhibited unique sets of upregulated ECM and cell adhesion genes in vivo, indicating cancer-specific interactions.
Conclusions:
- In vivo studies are crucial for understanding the specific contribution of cancer cells to the overall gene expression profile of a tumor.
- The tumor microenvironment profoundly modulates cancer cell gene expression, with distinct patterns emerging in vivo compared to in vitro culture.
