1996 Fiscal Year Final Research Report Summary
MOLECULAR BIOLOGICAL APPROACHES FOR IDENTIFYING CANCER METASTASIS-RELATING GENES
| Project/Area Number |
07670260
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Experimental pathology
|
|---|
| Research Institution | KANAZAWA MEDICAL UNIVERSITY |
|---|
Principal Investigator |
TANINO Mikio KANAZAWA MEDICAL UNIVERSITY,DEPARTMENT OF PATHOLOGY,ASSOCIATE PROFESSOR, 医学部, 助教授 (60135051)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TATSUKA Masaaki HIROSHIMA UNIVERSITY,DEPARTMENT OF REGULATORY RADIOBIOLOGY,ASSOCIATE PROFESSOR, 原爆放射能医学研究所, 助教授 (50216991)
OTA Takahide KANAZAWA MEDICAL UNIVERSITY,DEPARTMENT OF PATHOLOGY,ASSISTANT PROFESSOR, 医学部, 講師 (10152141)
|
|---|
| Project Period (FY) |
1995 – 1996
|
| Keywords | cancer metastasis / oncogene / ras / src / expression cloning / cell motility / early embryogenesis / metalloprotease |
|---|
| Research Abstract |
To identify cancer metastasis-related genes, we established a recipient cell (1-1ras 1000 originated from BALB/c 3T3 A31-1-1 clonal variant) system by utilizing the calcium phosphate-mediated genomic DNA transfer method. By using genomic DNAs from several human tumor cells, we detected an activity to confer metastatic phenotype to the nonmetastatic recipient cells upon the DNA transfection.
In another approach, we found that v-src-transformed BALB/c 3T3 A31-1-1 cells were highly metastatic whereas activated ras-transformed cells were nonmetastatic. It is supposed that src related-signal transduction cascade (s) are involved in the induction of metastatic ability. To identify this cascade (s), we examined the expression and the activity of membrane-type matrix metalloprotease (MT-MMP), known as a key enzyme to degradiate extracellular matrix protein and also known as a metastasis-related molecule. MT-MMP were not different between ras- and src-transformed A31-1-1 cells in culture, but there observed the increased expression and activity of MMP and MT-MMP in vivo tumor mass in src-transformed cells comparing to ras-transformed cells. This suggests that there is an apparent metastasis-inducing signal transduction system specific to in vivo.
Furthermore, we investigated the expression of MT-MMP during the development of mouse embryo with special attention to the neural crest cells. It was observed that the post-transcriptional regulation of the expression of MT-MMP were associated with the migration of these cells. We assume that the cell migration and tissue remodeling during development are suitable models for elucidating the mechanism of cancer metastasis.
|
