Background and objectives: TNF-alpha secreted by tumor cells and macrophages that have infiltrated into the micro-environment of a tumor may promote the metastasis of a variety of malignant cancers, including breast cancer. The present study was designed to detect gene expression changes in metastatic MCF-7 cells treated with a low dose of TNF-alpha (20ng/mL), and to further explore the mechanisms by which TNF-alpha can contribute to metastasis.
Methods: Transwell assays were performed to evaluate the invasive phenotype of MCF-7 cells. Samples for cDNA array analysis were collected 3h and 24h after pre-treatment with TNF-alpha and changes in gene expression were quantitated.
Results: The invasive phenotype of MCF-7 cells was enhanced by the exposure of MCF-7 cells to a low dose of TNF-alpha. Gene expression profiles of 39 genes significantly increased or decreased after treatment with TNF-alpha, 6 of which were genes not previously associated with regulation by TNF-alpha. Genes to promote metastasis, as well as to inhibit metastasis, were identified with some changes being time dependent.
Conclusions: TNF-alpha can enhance the invasive capacity of MCF-7 cells by affecting the expression of a group of genes that have roles in various steps of metastasis. Mechanistic insights into the role of TNF-alpha in tumor cell metastasis are discussed.