2000 Fiscal Year Final Research Report Summary
Cancer-Stromal Interaction in Lung Adenocarcinoma
| Project/Area Number |
10670223
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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 |
Experimental pathology
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| Research Institution | NATIONAL CANCER CENTER |
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Principal Investigator |
NIKI Toshiro National Cancer Center Research Institute, Pathology Division, Section Head, 病理部, 室長 (90198424)
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| Project Period (FY) |
1998 – 2000
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| Keywords | lung adenocarcinoma / VEGF / angiogenesis / invasion / matastasis / laminin / prognosis / RT-PCR |
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| Research Abstract |
The VEGF family is a group of growth factors that regulate the growth of endothelial cells. Studies suggest that VEGF-A is involved in tumor invasion and metastasis. We investigated the expression levels of VEGF-A, -B, -C, and -D in 60 cases of lung adenocarcinomas by quantitative RT-PCR analyses, and explored whether their expression levels were correlated with lymph node metastasis. We found that tumors with lymph node metastasis were associated with a pattern of low VEGF-D and high VEGF-A, VEGF-B, and VEGF-C.Also, levels of VEGF-A, but not of VEGF-B or VEGF-C, were higher in tumors with large nodal metastasis than in those with small nodal metastasis. These results are consistent with the hypothesis that two VEGF family members are involved at two distinct steps ; VEGF-C facilitates entry of cancer cells into lymph vasculature, whereas VEGF-A promotes the growth of metastatic tumor through angiogenesis.
Next, we immunohistochemically investigated the expression of laminin-5 in 102 cases of small lung adenocarcinomas. The laminin-5 protein is an extracellular matrix protein that is known to facilitate motility of cancer cells. Overall, laminin-5 expression was observed in 82 cases : 7 of 18 bronchiolo-alveolar carcinomas and 75 of 84 invasive adenocarcinomas. Laminin-5 was preferentially localized in the cytoplasm of tumor cells at the tumor-stromal interface, where budding or dissociation of cancer cells was frequently observed. Survival analysis revealed that over-expression of laminin-5 (24 cases, 23.5%) was an independent prognostic factor in both univariate and multivariate analyses. Further in vitro experiments showed that laminin-5 γ2 chain mRNA levels were correlated with erbB-2 expression and MAPK phosphorylation in lung adenocarcinoma cell lines. Treatment with TGF-α, HGF, TNF-α, and IL-1 β increased the laminin-5 γ 2 chain mRNA levels in a time-dependent manner.
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