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组织蛋白酶D对CD11b+髓系来源细胞体外增殖、迁徙和侵袭的影响及侵袭机制
作者:孙万里  周家华 
单位:东南大学附属中大医院 肝胆外科, 江苏 南京 210009
关键词:组织蛋白酶 D CD11b+髓系来源细胞 增殖 迁徙 基质金属蛋白酶-2 
分类号:R735.9;R33
出版年·卷·期(页码):2014·33·第四期(401-405)
摘要:

目的:探讨组织蛋白酶D(cathepsin D)对CD11b+髓系来源细胞(BMDCs)体外增殖、迁徙和侵袭的影响,并初步探索侵袭机制。方法:建立预转移期内胰腺癌原位瘤裸鼠模型L3.6pl组或Colo357组和无瘤荷裸鼠模型,流式细胞术检测骨髓和肝脏中CD11b+髓系来源细胞的比例,MTT检测细胞增殖能力,Transwell侵袭小室实验检测细胞的侵袭及迁徙能力,蛋白质印迹法检测分泌蛋白组织蛋白酶D的表达和CD11b+髓系来源细胞中基质金属蛋白酶2(MMP-2)的表达。结果:预转移期内胰腺癌原位瘤L3.6pl组骨髓和肝脏中CD11b+细胞比例明显高于Colo357组(P<0.05)。组织蛋白酶D可以促进CD11b+髓系来源细胞的增殖、迁徙和侵袭,而阻断组织蛋白酶D之后,细胞增殖、迁徙和侵袭则明显地受到抑制。组织蛋白酶D增强CD11b+髓系来源细胞中MMP-2的表达。结论:组织蛋白酶D在诱导CD11b+髓系来源细胞的增殖和迁徙中发挥重要作用,并通过对MMP-2的调控来增强CD11b+髓系来源细胞的体外侵袭能力。

Objective: To explor the effects of cathepsin D on proliferation,migration and invasion of CD11b positive bone marrow derived cells(BMDCs) in vitro and elucidate mechanism of invasion. Methods: Establish the orthotopic pancreatic cancer nude-mouse mode(L3.6pl group or Colo357 group) in pre-metastasis period and non-cancer nude-mouse mode, the rate of CD11b positive cells in the bone marrow and liver were tested by flow cytometry.The capability of cell proliferation were tested by MTT.The capability of cell migration and invasion were tested by Trans-well chamber invasion assay,the expression MMP-2 and CathepsinD protein were determined by western blot.Results: The rate of CD11b positive cells in L3.6pl group orthotopic pancreatic cancer nude-mouse mode bone marrow and liver were higher than those of Colo357 group in pre-metastatic period (P<0.05).Cathepsin D promoted CD11b+BMDCs proliferation,migration and invasion, and blocked Cathepsin D could inhibited the cell proliferation,migration and invasion. Cathepsin D enhanced MMP-2 expression of CD11b+BMDCs.Conclusion: Cathepsin D play an important role in induce CD11b positive bone marrow derived cells on proliferation and migration,it enhance invasion of CD11b positive bone marrow derived cells by regulated MMP-2.

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