| Project/Area Number |
17591736
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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 |
Obstetrics and gynecology
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| Research Institution | Osaka University |
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Principal Investigator |
YOSHINO Kiyoshi Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (90362730)
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| Co-Investigator(Kenkyū-buntansha) |
ENOMOTO Takayuki Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90283754)
FUJITA Masami Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 講師 (60303963)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | cervical cancer / 3^<rd> chromosome / TSC403 / LAMP3 / metastasis / invasion / 3番染色 / 子宮頚癌 |
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| Research Abstract |
LAMP3 (DC-LAMP, TSC403, CD208) was originally isolated as a gene specifically expressed in lung tissues. LAMP3 is located on a chromosome 3q segment that is frequently amplified in some human cancers, including uterine cervical cancer. Because two other members of the LAMP family of lysosomal membrane glycoproteins, LAMP1 and LAMP2,were previously implicated in potentially modulating the interaction of vascular endothelial and cancer cells, we hypothesized that LAMP3 might also play an important part in metastasis.
To clarify the metastatic potential of the LAMP3 in cervical cancers, we transfected a LAMP3-expression vector into a human uterine cervical cancer cell line, TCS. In an in vitro invasion assay, the migration of LAMP3-overexpressing TCS cells was significantly higher than in control TCS cells. In an in vivo metastasis assay, distant metastasis was detected in 9 of 11 LAMP3-overexpressing TCS-cell-injected mice and in only 1 of 11 control mice. Histological study showed that LAMP3-overexpressing cells readily invaded into the lymph-vascular space.
In clinical samples, quantitative real-time RT-PCR analyses showed that LAMP3 mRNA was significantly up-regulated in 47 of 47 (100%) cervical cancers and in 2 of 15 (13%) cervical intraepithelial neoplasias (CINs), compared to a low level of LAMP3 mRNA expressed in normal uterine cervixes. Interestingly, high LAMP3 expression was significantly correlated with the overall survival of patients with stage I/II cervical cancers.
These findings indicate that LAMP3 overexpression is associated with an enhanced metastatic potential, and may be a prognostic factor for cervical cancer.
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