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侵袭性密切相关。然而，37LBP 的详细作用尚未完全阐明。直接通过癌细胞中的37LBP，通过反义建立了37LBP表达减少的小鼠肺癌细胞系T11 RNA表达载体。当5x10@D15@>D1细胞皮下接种到同基因小鼠中时，T11受体的平均存活时间(77.0(]SY.+-.[)14.8天)比两者都显着延长。亲本细胞系 P29（34.8(]SY.+-.[)5.5 天）和正义 RNA 转染子 T42 （33.4(]SY.+-.[)4.2 天），（p<0.001）相同大小的接种肿瘤的免疫组织化学表明，T11 中的微血管密度显着低于 P29 和 T42 中观察到的微血管密度（p<0.05）。还表明，在条件培养基中培养的 T11 细胞的增殖和迁移显着降低（p<0.01）。与 P29 和 T42 相比，毛细血管内皮细胞的 37LBP 表达降低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

Abe, K・Sato, k et.al.: "Presence of atypical laminin on the surface of mouse Lewis lung careinoma cells" Tohoku J Exp Med. 180. 33-44 (1996)

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)

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。”

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

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”。