| Co-Investigator(Kenkyū-buntansha) |
URA Hideki SAPPORO MEDICAL UNIVERSITY SCHOOL OF MEDICINE ASCISTANT PROFESSOR, 医学部, 講師 (50264510)
SATO Takashi SAPPORO MEDICAL UNIVERSITY SCHOOL OF MEDICINE, ASOCIATE PROFESSOR, 医学部, 助教授 (50205928)
HIRATA Koichi SAPPORO MEDICAL UNIVERSITY SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (50136959)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
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| Research Abstract |
Though lymph node metastasis is very often encountered in patients with gastric cancer, the biological mechanism of lymph node metastasis is not clarified well, compared with hematogenous and peritoneal metastasis. The animal model of lymph node metastasis is rarely established and reported. We have already established highly liver metastatic mice model, AZ-H7d and peritoneal metastatic model, AZ-P7a, from the parental AZ-521 lines with a low potential of metastasis and investigated the mechanisms of these two types of metastasis. Our results suggested that enhanced expression of VEGF and α3-integrin in hematogenous metastasis, enhanced motile activity and α5-, α v β 5-integrins in peritoneal dissemination might play an important role in gastric cancer. At the basis of these experiments, we established novel mice model with high potential of lymph node metastasis, designated as AZ-L5G.In comparison with AZ-521, we investigated the biology implicated the development of lymph node metastasis. Then the entity that makes the biological differences of lymph node metastasis and hematogenous and/or peritoneal metastasis was investigated compared with AZ-H7d and AZ-P7a. Moreover, recent development of molecular biology revealed that a variety of genes were concerned with the cancer metastasis at their each steps. Using cDNA macroarray and DNA chip technologies, the relative mRNA levels of genes expressed in AZ-521 and AZ-L5G cell lines are identified. Moreover, we perform global analysis on different gene expression of AZ-521, AZ-H7d, AZ-P7a and AZ-L5G.This unique, in vivo model cell line might be highly useful to study the biology of metastasis of gastric cancer and our results lead to the development of new therapeutic modalities against human gastric cancer.
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