2006 Fiscal Year Final Research Report Summary
Molecular and clinical analysis for metastasis and invasion of cancers in small animals
| Project/Area Number |
15208030
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Clinical veterinary science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SASAKI Nobuo The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院農学生命科学研究科, 教授 (60107414)
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| Co-Investigator(Kenkyū-buntansha) |
TSUJIMOTO Hajime The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院農学生命科学研究科, 教授 (60163804)
NISHIMURA Ryohei The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院農学生命科学研究科, 教授 (80172708)
NAKAYAMA Hiroyuki The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院農学生命科学研究科, 教授 (40155891)
MORIMATSU Masami Hokkaido University, Graduate School of Medicine, Associate Professor, 大学院医学研究科, 助教授 (70241370)
MOCHIZUKI Manabu The University of Tokyo, Graduate School of Agriculture and Life Sciences, Associate Professor, 大学院農学生命科学研究科, 助教授 (90261958)
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| Project Period (FY) |
2003 – 2006
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| Keywords | canine mammary tumor cell line / feline mammary tumor cell line / canine mast cell tumor / adhesion molecule / retinoid / E-cadherin / microarray / metastasis / invasion |
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| Research Abstract |
In this study, we tried to analyze the mechanism of tumor metastasis and local invasion in small animals using 5 cell lines established in our laboratory.
In canine mammary cancer, expression and function of E-cadherin and catenin were compared between 4 pairs of cell lines established from the primary or metastatic lesions of the same patients. As a result, there were no differences in their expression but their function was higher in cell lines established from the metastatic lesions than those from primary lesions. This may indicate that the cells in the metastasis with low E-cadherin function are easily released from the primary lesions. In addition, sLe(x), an adhesion molecule to the endothelial cells, was alos highly expressed in one of the cell lines established from the thoracic effusion due to metastasis. Our previous data showed sLe(x) was 60% positive in the mammary tumor tissues, but not in normal mammary gland. From these data, sLe(x) may play a role in the metastasis of c
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anine mammary tumors. Currently one of this mammary tumor cells was cloned and microarray analysis was conducted to clarify the genetic change in the cells from primary and metastatic lesions in nude mice model. The result may suggest some important molecules including NfκB and hipoxia related one, which will be analyzed in the future.
In feline mammary tumors, we established 8 cell lines including 2 pairs from primary and metastatic lesions of the same patient. Using these cell lines, expression of a chemokine receptor CXCR4 and its ligand SDF-1 were compared between cell lines. Their expression was higher in those originated from metastasis than primary lesions, suggesting they may also play a role in tumor metastasis in feline mammary tumors. In addition, tumor-suppressing molecule, Braca2, was also analyzed in relation to the malignancy of this tumor.
Retinoids, vitamin A derivatives, may control the growth of canine mast cell tumors. This tumor growth-inhibitory effect of retinoids against canine mast cell tumors was mediated by a receptor RAR alpha and via inducing apoptosis in both in vitro model and in vivo nude mice model, as in human acute promyelocytic leukemia. These results suggest the retinoids may be a potential chemotherapeutic agent for canine mast cell tumors. For canine osteosarcoma, gene therapy using wild type p53 transfection using adenovirus as a vector virus. This trial showed some efficacy in nude mice model and even in the canine patients with ostesarcoma. For canine melanoma, spindle check point function is currently investigated to analyze its relationship to chemotherapeutic response of the tumor. Less
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