In this way, we derived a gene signature specific to breast cancer migration and invasion, which we call the Human Invasion Signature (HIS). Here, we used this assay in orthotopic xenografts of human MDA-MB-231 breast cancer cells to isolate selectively the migratory cell subpopulation of the primary tumor for gene-expression profiling. In the past, we developed an in vivo invasion assay that can capture specifically the highly motile tumor cells in the act of migrating inside living tumors. Therefore, little information is available about the crucial early steps of the metastatic cascade: migration, invasion, and entry of tumor cells into the systemic circulation. When whole tissue is used for molecular profiling, the expression pattern of these cells is masked by the majority of the noninvasive tumor cells. In reality, only a small subpopulation of invasive cells inside the primary tumor is responsible for escaping and initiating dissemination and metastasis. However, these were derived mostly from whole tissue without respect to cell heterogeneity. Previous genome-wide studies have identified gene-expression patterns correlated with cancer patient outcome. Metastasis of breast cancer is the main cause of death in patients.
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