Expression of laminin binding protein (37LBP/p40) and tumor angiogenesis in lung cancer

肺癌中层粘连蛋白结合蛋白（37LBP/p40）的表达与肿瘤血管生成

• 批准号: 08457178
• 负责人: SATOH Ken
• 金额: $ 2.11万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457178/
• 关键词: 37-kDa; Laminin; Receptor; Angiogenesis; Lung Cancer; Gene Therapy; Antisense RNA; ラミニンレセプター; 腫瘍血管; マウス; アンチエンスRNA; レトロウイルスベクター

Expression of the 37-kDa laminin binding protein (37LBP), a precursor protein of the 67-kDa laminin receptor, correlates well with biological aggressiveness of cancer cells. However, the detailed role of 37LBP is not fully understood. To elucidate the role playd by the 37LBP in cancer cells directly, a murine lung cancer cell line T11, in which 37LBP expression was remarkably diminished, was established by an antisense RNA expression vector. When 5x10<@D15@>D1 cells were subcutaneously inoculated into syngenic mice, the mean survival time of T11-recipient (77.0(]SY.+-。[)14.8 days) was significantly prolonged compared with that of both the parental cell line P29 (34.8(]SY.+-。[)5.5 days) and the sense RNA-transfectant T42 (33.4(]SY.+-。[)4.2 days), (p<0.001). Immunohistochemistry of inoculated tumors of the same size demonstrated that microvessel density in T11 was significantly lower than that observed in both P29 and T42 (p<0.05). It was also shown that T11 cells cultured in a conditioned medium exhibited signiflcantly reduced proliferation (p<0.01) and migration (p<0.05) of the capillary endothelial cells compared with P29 and T42. These results suggest that decreased expression of 37LBP in T11 may relate to its low tumorigenicity, and that this may be partly caused by diminished tumor angiogenesis of the murine lung cancer.

37 kDa层粘连蛋白结合蛋白(37LBP)是67 kDa层粘连蛋白受体的前体蛋白，其表达与癌细胞的生物学侵袭性密切相关。然而，37LBP的详细作用尚不完全清楚。为了直接阐明37LBP在肿瘤细胞中的作用，用反义RNA表达载体建立了37LBP表达显著下调的小鼠肺癌细胞系T11。用5×10~(-1)×10~(-1)×10~(-1)~(-1)D15~(-1)细胞皮下接种同基因小鼠，T11~-受体的平均存活时间为(77.0±+)。[)14.8天)较亲本细胞系P29(34.8()sy.+-)显著延长。[)5.5天)和正义RNA转染体T42(33.4()sy.+-.[)4.2d)，(p&lt；0.001)。免疫组织化学结果显示，T11的微血管密度明显低于P29和T42(p&lt；0.05)。与P29和T42相比，在条件培养液中培养的T11细胞对毛细血管内皮细胞的增殖(p&lt；0.01)和迁移(p&lt；0.05)均有显著的抑制作用。这些结果提示，37LBP在T11中的低表达可能与其低致瘤性有关，这可能部分是由于小鼠肺癌的肿瘤血管生成减少所致。

项目成果

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Abe, K. Sato, k 等：“小鼠 Lewis 肺癌细胞表面存在非典型层粘连蛋白”Tohoku J Exp Med 180. 33-44 (1996)

Yaekashiwa M,Nakyama S,Ohnuma K,Sakai T,Abe T,Satoh K,Matsumoto K,Nakamura T,Takahashi T,Nakiwa T.: "Simultaneous or delayd administration of hepatocyte growth factor (HGF) equally represses the fibrotic changes in murine lung injury induced by bleomycine

Yaekashiwa M、Nakyama S、Ohnuma K、Sakai T、Abe T、Satoh K、Matsumoto K、Nakamura T、Takahashi T、Nakiwa T.：“同时或延迟施用肝细胞生长因子 (HGF) 同样可以抑制小鼠的纤维化变化

Hara K,Satoh K,Ide H.: "Atypical ectodermal ridge dependent expression of the 67kDa laminin binding protein (clbp) gene in developing chick limb bud." Zool Science. 14. 969-978 (1997)

Hara K、Satoh K、Ide H.：“发育中的小鸡肢芽中 67kDa 层粘连蛋白结合蛋白 (clbp) 基因的非典型外胚层嵴依赖性表达。”

Abe K,Murakami S,Mukae N,Mita T,Hashimoto Y,Isemura M,Shimo-oka M,Ii K,Kitamura K,Narumi K,Satoh K,Nukiwa T.: "Presence of atypical laminin on the surface of mouse Lewis lung carcinoma cells." Tohoku J Exp Med. 180. 33-44 (1996)

Abe K、Murakami S、Mukae N、Mita T、Hashimoto Y、Isemura M、Shimo-oka M、Ii K、Kitamura K、Narumi K、Satoh K、Nukiwa T.：“小鼠 Lewis 表面存在非典型层粘连蛋白

Hara K, SAtoh K, et al.: "Apical Ectodermal Ridge-Depundent Expression of the chick 67 KDa Laminin Binding Pnoteui geue in Devecloping Limb Bud." Zool Science. 14. 969-978 (1997)

Hara K、SAtoh K 等人：“小鸡 67 KDa 层粘连蛋白结合 Pnoteui geue 在发育肢芽中的顶外胚层脊依赖性表达”。