Differential metastasis-related gene analysis of prostate cancer cells isolated from primary tumor and spontaneous metastases in nude mice with orthotopic injection of PC-3M cells by cDNA microarray / 中国癌症杂志

ABSTRACT

Background and Purpose:Prostate cancer is one of the most common cancers and the second leading cause of cancer-related death in Europan and North American males.The incidence of prostate cancer has also been increasing during the past few decades in China.It is widely accepted that this heterogeneity,which results from the tumor progression driven largely by genomic instability(genetic and/or epigenetic alterations)of tumor cells in primary tumor,endows specific populations of tumor cells with the unique character needed for invasion,migration,and metastasis colony formation in other organs and only these subpopulations possessing thost character can survive the potentially destructive journey from the primary tumor to the sites of metastases.The purpose of the present study was to explore the genes associated with invasion and metastasis of human prostate cancer cell line PC-3M in nude mice.Methods:After PC-3M cells were inoculated into orthotopic site(prostate) in a male nude mouse for two months,tumor cells were isolated from the primary tumor and lymph node metastasis,separately.Cell invasion and adhesion ability in vitro were first compared between two cells.Then metastasis-related genes differentially expressed between them were analyzed by utilizing cDNA microarray technique.Results:The in vitro cell invasion and adhesion potential of tumor cells from lymph node metastasis was significantly higher than those from primary tumor by 2.5 fold and 1.5 fold,respectively.Metastasis-related genes differentially expressed between those two sublines were identified,all of them were up-regulated in the tumor cells from lymph node metastasis and could be categorilized 1.genes encoding cellular matrix-degrading proteolytic enzyme including cathepsin and MMP.2.genes encoding transcription factors.3.genes related to heterotypic adhesion of tumor cells.4.genes encoding cell surface receptors.Conclusions:There are significant differences in invasion and adhesion potential between cells from primary tumor and those from lymph node metastasis.Some differentially expressed molecules might be playing pivotal roles in promoting tumor cells to migrate from primary tumors to distant metastases,which may be helpful to elucidate the possible mechanism of metastasis in prostate cancer.