| Project/Area Number |
18590320
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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 | Chiba University |
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Principal Investigator |
FURUYA Mitsuko Chiba University, Graduate School of Medicine, Assistant Professor (10361445)
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| Co-Investigator(Kenkyū-buntansha) |
KASUYA Yoshitoshi Chiba University, Graduate School of Medicine, Associate Professor (70221877)
SUGIURA Tsuyoshi Kushu University, Hospital, Assistant Professor (40322292)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,020,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | tumor / metastasis / invasion / extracellular matrix / tetraspanin / integrin / cytoskeleton / signal transduction |
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| Research Abstract |
We showed that the expression levels of CD151 and its associated integrin subunits in epidermal carcinoma cell HSC5 were higher than those in immortalized epidermal cell HaCaT. By the stimulation of epidermal growth factor, CD151 was dissociated from cell surface and dispersed in the cytoplasm, and a3b1 integrin was concomitantly internalized. To understand the significance of CD151 in tumor cell dynamics, CD151 in HSC5 was knocked down (HSC5CD151KO), and the expression of integrin subunits and matrix metalloproteinases (MMPs) were investigated. In HSC5CD151KO, striking morphological alteration on Matrigel and laminin, and cytoskeletal rearrangements were demonstrated. A3b1 integrin was internalized in part, and a6b4 integrin was re-distributed from basal site to cell periphery. Quantitative RT-PCR, Western blot and zymography revealed that the expression levels of MMP2, MMP7 and MMP9 were markedly downregulated in HSC5CD151KO. Immunoprecipitation assay demonstrated that MMP7 was co-immunoprecipitated with CD151. In double stainings, MMP7 was colocalized with CD151 at the leading edge of lamellipodia under migratory status. These results elucidated the importance of CD151 as one of the key molecules for integrin-dependent carcinoma-stroma interaction. It is indicated that CD151 might contribute not only to cell stabilization by associating with adhesion complexes but also to cell migration by inducing integrins re-localization and MMPs production.
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