Cancer-Stromal Interaction in Lung Adenocarcinoma

肺腺癌中的癌症-间质相互作用

• 批准号: 10670223
• 负责人: NIKI Toshiro
• 金额: $ 1.54万
• 依托单位: NATIONAL CANCER CENTER
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670223/
• 关键词: lung adenocarcinoma; VEGF; angiogenesis; invasion; matastasis; laminin; prognosis; RT-PCR; 予後因子; VEGF; 血管新生

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.

VEGF家族是一组调节内皮细胞生长的生长因子。研究表明VEGF-A参与肿瘤的侵袭和转移。我们通过定量RT-PCR分析了60例肺腺癌中VEGF-A、-B、-C和-D的表达水平，并探讨其表达水平是否与淋巴结转移相关。我们发现，有淋巴结转移的肿瘤与低 VEGF-D 和高 VEGF-A、VEGF-B 和 VEGF-C 模式相关。此外，大淋巴结转移的肿瘤中 VEGF-A 的水平高于小淋巴结转移的肿瘤，但 VEGF-B 或 VEGF-C 的水平则不然。这些结果与两个 VEGF 家族成员参与两个不同步骤的假设相一致； VEGF-C 促进癌细胞进入淋巴管系统，而 VEGF-A 通过血管生成促进转移性肿瘤的生长。 接下来，我们采用免疫组化方法研究了 102 例小肺腺癌中层粘连蛋白 5 的表达。 Laminin-5 蛋白是一种细胞外基质蛋白，已知可促进癌细胞的运动。总体而言，在 82 例病例中观察到层粘连蛋白-5 表达：18 例细支气管肺泡癌中的 7 例和 84 例浸润性腺癌中的 75 例。 Laminin-5优先定位于肿瘤-基质界面处的肿瘤细胞的细胞质中，经常观察到癌细胞的出芽或解离。生存分析显示，在单变量和多变量分析中，laminin-5 的过度表达（24 例，23.5%）是一个独立的预后因素。进一步的体外实验表明，肺腺癌细胞系中层粘连蛋白5γ2链mRNA水平与erbB-2表达和MAPK磷酸化相关。 TGF-α、HGF、TNF-α 和 IL-1 β 治疗以时间依赖性方式增加了层粘连蛋白-5 γ 2 链 mRNA 水平。

项目成果

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)

Yasumitu Moriya、Toshiro Niki 等人：“层粘连蛋白 5 的表达增加及其在小尺寸肺腺癌中的预后意义”癌症。