Establishment of hepatic metastasis model of pancreatic carcinoma and it application to the development of therapeutic agents

1.检测人胰腺癌细胞系（MIA PaCa-2、Hs 776 T、PANC-1、MDA Panc 3、MDA Panc 28、SU 86.86、HPAF-II、AsPC-1、Capan-1和HPAC）在无胸腺裸鼠脾内注射后产生肝转移灶的能力。只有四个细胞系（HPAF-II，AsPC-1，Capan-1和HPAC）显示产生肝转移。对这四种细胞系进行体内选择，以在脾内注射后增加转移潜能。然而，从转移瘤中长出的细胞并没有显示出转移潜能的增加.由于这四种细胞系（HPAF-II、AsPC-1、Capan-1和HPAC）显示在胰腺内移植后转移至肝脏，因此还进行了原位移植的体内选择。高转移性变异体，没有产生这种选择。这些结果表明，高转移性胰腺癌的细胞和分子决定因素的特点， ...更多信息 应该通过从这四种高转移性变体细胞系中选择低转移性变体来进行细胞的筛选。此外，建议这四个转移细胞和其余（六个细胞系）之间的比较应该被证明是有用的。使用表达阵列比较了一对相邻的非侵袭性和高侵袭性肿瘤的病理标本的基因表达。9个基因（MAP激酶激酶-5、原癌基因c-src、聚集蛋白聚糖1、硫酸软骨素核心蛋白-1、Visican isohomes、BM-40、血小板反应蛋白-1前体、TIMP-1、前胶原C蛋白）在非侵袭性肿瘤中的表达水平高于邻近侵袭性肿瘤。然而，当比较9个病理标本时，浸润性肿瘤中的表达水平并不总是很低，即非浸润性和高度恶性胰腺癌细胞之间的差异表达并不总是如此.得克萨斯大学M。D.安德森癌症中心建立了人胰腺癌细胞COLO 357的高转移性变异细胞。这些细胞系之一，L3.6pl细胞，被证明是更大的转移后原位移植到裸鼠胰腺比亲本FG细胞。作为一项合作努力，这两种细胞之间的基因表达水平的差异通过Takara Intelligene微阵列进行了检查。发现33个基因在L3.6pl细胞中的表达比亲本FG细胞高3倍以上。少

1. Human pancreatic carcinoma cell lines (MIA PaCa-2, Hs776T, PANC-1, MDA Panc 3, MDA Panc 28, SU86.86, HPAF-II, AsPC-1, Capan-1, and HPAC) were tested for their capacity to generate hepatic metastataic following intrasplenic injections in athymic nude mice. Only four cell line (HPAF-II, AsPC-1, Capan-1, and HPAC) were shown to produce hepatic metastasis. These four cell lines were subjected to in vivo selections for increased metastatic potentials following intrasplenic injections. However, cells grown out from metastases did not show increase in the metastatic potential.2. Because these four cell lines (HPAF-II, AsPC-1, Capan-1, and HPAC) were shown to metastasize to the liver after intra-pancreatic transplantations, in vivo selections with the orthotopic transplantation were also conducted. Highly metastatic variants, were not generated by this selection.3. These results indicated that characterization of cellular and molecular determinants of highly metastatic pancreatic carcinoma … More cells should be conducted through selections of poorly metastatic variants from these four highly metastatic variant cell lines. Also, it is suggested that comparisons between these four metastaic cells and rest (six cell lines) should prove to be useful.4. A pair of pathological specimens from noninvasive and highly invasive tumors adjacent to each other was compared for the gene expression by the use of expression arrays. Nine genes (MAPkinase kinase-5、 protooncogene c-src、 aggrecan 1、chondroitin sulfate coreprotein-1、Visican isohomes、BM-40、thrombospondin-1 precursor、TIMP-1、procollagen C-protein) were identified to be higher in the expression level in the non-invasive tumor than in the adjacent invasive tumor. However, the levels were not always low in the invasive tumors when nine pathological specimens were compared, i.e. the differential expression between non-invasive and highly malignant pancreatic carcinoma cells was not always the case.5. Dr. Isaiah J. Fidler's group at the University of Texas M. D. Anderson Cancer Center established highly metastatic variant cells of human pancreatic COLO357 carcinoma cells. One of these cell lines, L3.6pl cells, was shown to be more metastatic after orthotopic transplantation into pancreas of nude mice than the parental FG cells. As a collaborative effort, difference in the level of gene expression between these two cells was examined by Takara Intelligene Microarray. Thirty three genes were found to be expressed more than three times higher in L3.6pl cells as compared to parental FG cells. Less