利用基因芯片法探索人前列腺癌细胞PC-3M在裸鼠体内淋巴道转移相关基因

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背静与目的:前列腺癌是欧美国家最常见的一种男性恶性肿瘤,近年来在我国该病也有明显上升趋势。目前认为肿瘤转移是由于一部分肿瘤细胞在肿瘤生长过程中发生基因水平的变化而改变性质变成“转移克隆的细胞”,这部分细胞能突破机体防御系统最终到达远处组织器官形成转移灶。本实验旨在探索人前列腺癌细胞PC-3M在裸鼠体内淋巴道转移的相关基因,为进一步研究前列腺癌淋巴道转移机制打下一定的基础。方法:将PC-3M细胞原位接种于裸鼠体内两个月后分别从原发灶和淋巴结转移灶分离肿瘤细胞,通过体外侵袭和粘附实验,比较两者体外侵袭和粘附能力的差异,并应用基因芯片技术,检测两细胞在转移相关基因丰度水平上的差异。结果:淋巴结转移灶分离的肿瘤细胞的体外侵袭及粘附能力显著高于原发灶内分离的肿瘤细胞,大约分别为后者的2.5倍和1.5倍;而且前者在一些转移相关基因丰度水平上明显高于后者,这些基因按其编码产物的属性和功能可划分为:①编码降解细胞外基质(ECM)的蛋白水解酶包括组织蛋白酶、基质金属蛋白酶;②编码转录因子家族成员;③编码参与肿瘤细胞异质性粘附的分子;④编码细胞表面受体。结论:原发灶内的前列腺癌细胞和淋巴结转移灶内的肿瘤细胞在侵袭和粘附能力上存在显著差异,经鉴定的差异表达分子可能在前列腺癌细胞由原发灶迁移到远处组织器官的转移过程中发挥重要作用。 Back and Objective: Prostate cancer is the most common form of male malignant tumors in Europe and the United States. In recent years, the disease has also shown a clear upward trend in our country. Now that the tumor metastasis is due to part of the tumor cells in the tumor growth process changes in the gene level and change the nature of the “cloned cells”, this part of the cell can break through the body defenses eventually reach distant organs and metastases. The purpose of this study is to explore the related genes of human prostate cancer cell PC-3M in lymphatic metastasis in nude mice, which will lay a foundation for further study of lymphatic metastasis of prostate cancer. Methods: PC-3M cells were inoculated in situ into nude mice for two months and then the tumor cells were separated from the primary tumor and lymph node metastasis respectively. The invasion and adhesion ability of PC-3M cells in vitro were compared by in vitro invasion and adhesion experiments , And using gene chip technology to detect differences in the abundance of metastasis-related genes between the two cells. Results: In vitro invasion and adhesion of tumor cells isolated from lymph node metastasis were significantly higher than those isolated from primary tumor, which were about 2.5 times and 1.5 times that of the latter respectively. Moreover, Were significantly higher than the latter, these genes according to the properties and functions of their encoded products can be divided into: ① encoding degradation of the extracellular matrix (ECM) proteases including cathepsin, matrix metalloproteinases; ② encoding transcription factor family members; ③ Encodes molecules involved in the heterogeneous adhesion of tumor cells; and ④ encodes cell surface receptors. CONCLUSIONS: There are significant differences in invasion and adhesion between prostate cancer cells and lymph node metastasis in primary tumor. The differentially expressed molecules identified may migrate from primary tumor to distant tissues and organs in prostate cancer cells The transfer process plays an important role.
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