Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Urology. 2010 Mar;75(3):742-9. doi: 10.1016/j.urology.2009.03.008. Epub 2009 Aug 3.
To reveal the gene expression profile and pathways involved in host-tumor interactions in a rat orthotopic syngeneic bladder cancer model.
Rat bladder cancer cells (AY-27 cell line) were inoculated intravesically into female Fischer rats. The bladders were analyzed at 7, 14, and 28 days by histologic examination and at 14 days with Affymetrix GeneChip with a newly developed bioinformatics program for the Kyoto Encyclopedia of Genes and Genomes (KEGG).
The cancer had developed into Stage Ta and carcinoma in situ (Tis) after 7 days, Stage T1 after 14 days, and Stage T3 after 28 days in the bladder. At 14 days, >4000 genes were found to be differentially expressed and 20 KEGG pathways were actively involved in the bladder. The molecular pathway for (human) bladder cancer development was activated, and, at the same time, pathways in connection with the host immune responses were altered, including antigen processing and presentation, the T-cell receptor signaling pathway, natural killer cell-mediated cytotoxicity, the Toll-like receptor signaling pathway, and the B-cell receptor signaling pathway. Moreover, the cell adhesion molecules associated with the immune system were upregulated, but those associated with the neural system were downregulated.
The bladder cancer developed aggressively despite active host immune responses. Conceivably, the cancer immunoediting process is associated with the progression of bladder cancer in this model.
揭示在大鼠原位同基因膀胱癌模型中涉及宿主-肿瘤相互作用的基因表达谱和途径。
将大鼠膀胱癌细胞（AY-27 细胞系）经膀胱内接种到雌性 Fischer 大鼠中。在第 7、14 和 28 天通过组织学检查进行分析，并在第 14 天使用 Affymetrix GeneChip 和新开发的京都基因与基因组百科全书（KEGG）生物信息学程序进行分析。
在第 7 天，癌症已发展为 Ta 期和原位癌（Tis），在第 14 天发展为 T1 期，在第 28 天发展为 T3 期。在第 14 天，发现 >4000 个基因差异表达，20 个 KEGG 途径被积极参与膀胱。（人类）膀胱癌发展的分子途径被激活，同时与宿主免疫反应相关的途径发生改变，包括抗原加工和呈递、T 细胞受体信号通路、自然杀伤细胞介导的细胞毒性、Toll 样受体信号通路和 B 细胞受体信号通路。此外，与免疫系统相关的细胞粘附分子上调，但与神经系统相关的细胞粘附分子下调。
尽管存在活跃的宿主免疫反应，膀胱癌仍呈侵袭性发展。可以想象，癌症免疫编辑过程与该模型中膀胱癌的进展有关。
