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Cancer-Stromal Interaction in Lung Adenocarcinoma

Research Project

Project/Area Number 10670223
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionNATIONAL CANCER CENTER

Principal Investigator

NIKI Toshiro  National Cancer Center Research Institute, Pathology Division, Section Head, 病理部, 室長 (90198424)

Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Keywordslung adenocarcinoma / VEGF / angiogenesis / invasion / matastasis / laminin / prognosis / RT-PCR / 予後因子 / VEGF / 血管新生
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.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Toshiro Niki, et al.: "Expression of vascular endothelial growth factors A, B, C, and D and their relationships to lymph node status in lung adenocarcinoma"Clin Cancer Res. 6. 2431-2439 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toshiro Niki, et al.: "Expression of vascular endothelial growth factor receptor 3 in blood and lymphatic vessels of lung adenocarcinoma"J Pathol. (In press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yasumitu Moriya,Toshiro Niki, et al.: "Increased expression of laminin-5 and its prognostic significance in lung adenocarcinomas of small size"Cancer. (In press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toshiro Niki, et al.: "Expression of vascular endothelial growth factors A, B, C, and D and their relationships to lymph node status in lung adenocarcinoma."Clin Cancer Res. Vol. 6. 2431-2439 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toshiro Niki, et al: "Expression of vascular endothelial growth factor receptor 3 in blood and lymphatic vessels of lung adenocarcinoma."J Pathol. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yasumitu Moriya, Toshiro Niki, et al: "Increased expression of laminin-5 and its prognostic significance in lung adenocarcinomas of small size."Cancer. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toshiro Niki, et al.: "Expression of vascular endothelial growth factors A, B, C, and D and their relationships to lymph node status in lung adenocarcinoma"Clin Cancer Res. 6. 2431-2439 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Toshiro Niki, et al.: "Expression of vascular endothelial growth factor receptor 3 in blood and lymphatic vessels of lung adenocarcinoma"J Pathol. (In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yasumitu Moriya,Toshiro Niki, et al.: "Increased expression of laminin-5 and its prognostic significance in lung adenocarcinomas of small size"Cancer. (In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Niki T. et al.: "Expression of vascular endothelial growth factor-A, -B, -C, and -D and its relationship to lymph node status in lung adenocarcinoma"Clin Cancer Res. (in press). (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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