| Co-Investigator(Kenkyū-buntansha) |
HONMA Toshio SAPPORO MEDICAL UNIVERSITY SCHOOL OF MEDICINE, INSTRUCTOR, 医学部, 助手 (30315494)
URA Hideki SAPPORO MEDICAL UNIVERSITY SCHOOL OF MEDICINE, ASSIST.PROF., 医学部, 講師 (50264510)
HIRATA Koichi SAPPORO MEDICAL UNIVERSITY SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (50136959)
伝野 隆一 札幌医科大学, 医学部, 助教授 (40163943)
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| Research Abstract |
We established novel gastric cancer sublines (AZ-H5c, NUGC-3H5, TMK-1H7) and pancreatic cancer sublines (HPC-1H5, HPC-3H4, HPC-4H4, Panc-1H5) with a high potential for liver metastasis, and AZ-P7a, NUGC-3P4T, TMK-1P4a (gastric lines) and HPC-1P5a, HPC-3P4a, HPC-4P4a, Panc-1P5a (pancreatic lines) with a high potential for peritoneal metastasis derived from parental low-metastatic AZ-521, NUGC-3, THK-1, HPC-1, HPC-3, HPC-4 and Panc-1 cell lines, respectively. Using these established cell lines, we investigated the biological properties in hematogenous and peritoneal metastasis. Our studies suggested that hematogenous metastasis and peritoneal dissemination have assured biological differences. Moreover, angiogenetic factors in hematogenous metastasis and enhanced motile activity in peritoneal dissemination were closely implicated in the development of these two types of metastasis in digestive cancer. In addition, to clarify the molecular mechanisms of cancer metastasis and of the differe
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nt levels of gene expression in a variety of metastatic potentials in digestive cancer, differential gene expression analysis between parental cell lines and metastatic sublines, and between the metastasis sublines were performed.
We analyzed thousands of expressed genes in each cell line by DNA chip. In comparison with each parental cell lines, a large number of genes were up regulated or down-regulated in the cell lines highly metastatic to the liver and peritoneum. In addition, in pancreatic cancer, gene expression profiling analysis clarified 22 genes including FGF-5, matrilysin and so on, that could be used to classify the liver and peritoneal metastases. In gastrice cancer, 24 genes, Integrin3, cadherin and so on, were distinguished to classify the liver and peritoneal metastases.
Further studies should be needed to understand more thoroughly the involvement of angiogenetic factors, motile activity and differential expressed genes in cancer metastasis. However, these results will help to clarify the biological and molecular mechanisms of digestive cancer metastases. Moreover, genes revealed by profiling analysis will be novel molecular markers to predict whether some pancreatic and/or gastric cancers develop liver or peritoneal metastasis after curative resection. Less
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