2003 Fiscal Year Final Research Report Summary
Analysis of molecular mechanisms of basement membrane destruction in the process of lung cancer cell invasion
| Project/Area Number |
13670166
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
AKASHI Takumi Tokyo Medical and Dental University, University Hospital, associated Professor, 医学部附属病院, 講師 (60242202)
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| Project Period (FY) |
2001 – 2003
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| Keywords | lung cancer / adnocarcinoma / invasion / basement membrane / cytokine / cancer stromal interactin |
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| Research Abstract |
In the process of lung cancer invasion to the neighboring extracellular matrix, basement membrane is quite often disrupted. For the explanation of this, in addition to the inhibition of cancer cell invasion, we hypothesized that basement membrane sequester the cytokine diffusion secreted by the cancer cells and stimulating the growth of fibroblasts which promote the invasive natures of cancer cells.
We showed that lung cancer cell lines stimulated growth of fetal lung fibroblasts. bFGF and PDGF were the one of the growth stimulators in the cancer cell conditioned media. Basement membrane matrix significantly sequestered the diffusion of bFGF by the affinity binding to the heparin sulfate. bFGF were stored in the basement membrane matrix at higher concentration and the possibility of its release secondary to the basement membrane destruction.
In the other hand, basement membrane matrix inhibit the invasive growth of HGF-dependent invasion of A549 cells. By the cDNA array method, we examined the change of gene expression pattern of A549 cells in the existence of basement membrane matrix. We found that expression of 50 genes, including EF(elongation factor)1a1, EF1a2, EF1d,were significantly suppressed in the existence of basement membrane matrix. EF(elongation factor)1a1, EF1a2, EF1d were known to bind to f-actin and possibly regulate the celuular motility. Our results suggest that basement membrane inhibits the invasive nature of cancer cells via the suppression of elongation factor genes.
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