Differential metastasis-associated gene analysis of prostate carcinoma cells derived from primary tumor and spontaneous lymphatic metastasis in nude mice with orthotopic implantation of PC-3M cells.
The purpose of these studies was to explore the genes associated with invasion and metastasis of human prostatic carcinoma line PC-3M in nude mice. After PC-3M cells were inoculated in orthotopic site (prostate) in male nude mice for two months, tumor cells were isolated from primary tumor and lymph node metastasis in the same mouse, respectively. Cell invasion and adhesion ability in vitro were first compared between two cell lines. Then human metastasis-related genes differentially expressed between them were analyzed by utilizing cDNA microarray technique. The in vitro cell invasion and adhesion potential of tumor cells from lymph node metastasis was significantly higher than those from primary tumor, Metastasis-related genes differentially expressed between those two cell lines were identified, all of them were up-regulated in the tumor cells from lymph node metastasis and could be categorized as: (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. Moreover, Four genes were chosen for semi-quantitative RT-PCR analysis, they showed a consistent expression pattern with that of cDNA microarray analysis. We concluded that the lymph node metastasis in nude mice given an injection of PC-3M cells in the prostate is a selective process favoring the survival and growth of a special subpopulation derived from primary tumor with specific genetic alterations, which may play a pivotal role in the metastasis of prostate cancer. Identification and further characterization of these genes may allow a better understanding of lymphatic metastasis in prostate carcinoma.
Chu
Jian Hong
JH
Department of Pharmacology and Toxicology, Shanghai Institute of Planned Parenthood Research, Fudan University. National Evaluation Center for the Toxicology of Fertility and Regulating Drugs, Shanghai, 200032, P.R. China.
Sun
Zu Yue
ZY
Meng
Xue Lian
XL
Wu
Jian Hui
JH
He
Gui Lin
GL
Liu
Gui Ming
GM
Jiang
Xiu Rong
XR
D000818:Animals; D002403:Cathepsins / Q000235:genetics / Q000502:physiology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000502:physiology; D053504:Matrix Metalloproteinases, Membrane-Associated; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000235:genetics*; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002403:Cathepsins; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated