2004 Fiscal Year Final Research Report Summary
Expression of tetraspanins in human lung cancer cells : frequent downregulation of CD9 and its contribution to cell motility in small cell lung cancer
| Project/Area Number |
15590807
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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 |
Respiratory organ internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
KAWASE Ichiro Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (10161324)
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| Co-Investigator(Kenkyū-buntansha) |
TACHIBANA Isao Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (60324761)
OSAKI Tadashi Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (50324778)
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| Project Period (FY) |
2003 – 2004
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| Keywords | lung cancer / tetraspanin / CD9 / integrin / metastasis / cell motility / cell adhesion |
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| Research Abstract |
Small cell lung cancer (SCLC) invades locally and metastasizes distantly extremely early when compared with non-small cell lung cancer (NSCLC). The underlying molecular mechanisms, however, have not been elucidated. Accumulating evidence suggests that down-regulation of several members of tetraspanins is associated with progression of solid tumors, thus indicating poor prognosis. Here we screened 30 lung cancer cell lines for expression of tetraspanins, CD9,CD63,CD81,CD82,CD151, and NAG-2. Flow cytometry revealed that, among these proteins, CD9 is broadly expressed in NSCLC lines, but is absent or highly reduced in most SCLC lines (p<0.0001). Using the Boyden chamber and videomicroscopic cell motility assays, we showed that stable transfection of CD9 into a SCLC line, OS3-R5, reduced cell motility on fibronectin. Furthermore, by transient transfection of green fluorescent protein (GFP)-tagged CD9 into three other SCLC lines, we observed that SCLC cells expressing GFP-CD9 were uniformly less motile than untransfected cells. CD9 or GFP-CD9 was associated with b1integrins and distributed at the tumor cell periphery and cell-cell contacts, suggesting that CD9 modifies b1 integrin function to reduce motility. These findings suggest that low expression of CD9 may contribute to the highly invasive and metastatic phenotype of SCLC.
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Research Products
(3 results)
