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Cell Population Analyses During Skin Carcinogenesis
Published on: August 21, 2013
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由骨髓衍生细胞供应的MMP-9有助于皮肤癌发生
L M Coussens1, C L Tinkle, D Hanahan
1Cancer Research Institute, University of California, San Francisco 94143, USA. coussens@cc.ucsf.edu
Cell
|November 18, 2000
概括
矩阵金属蛋白酶MMP-9通过促进角质细胞的过度增殖,促进皮肤癌的发展. 然而,它的缺失导致更具侵略性的瘤,突出炎症细胞.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 皮肤病学 皮肤病学
背景情况:
- 矩阵金属蛋白酶MMP-9 (凝酶B) 与皮肤癌的进展有关.
- 它在由HPV16瘤基因诱导的多阶段表皮瘤发生中的作用需要进一步阐明.
研究的目的:
- 在小鼠模型中调查MMP-9对状癌发生的特定贡献.
- 确定参与瘤发育的MMP-9的细胞来源.
主要方法:
- 使用了缺乏MMP-9和HPV16瘤基因的转基因小鼠.
- 采用骨髓移植来制造具有选择性MMP-9表达在血液细胞中的嵌合体小鼠.
- 分析了角质细胞的增殖,分化和瘤入侵.
主要成果:
- 缺乏MMP-9的小鼠表现出较低的角质细胞过度增殖和较少的侵入性瘤.
- 缺乏MMP-9的小鼠的癌症显示出更大的差异化损失,表明更高等级和更具侵略性的瘤.
- MMP-9主要表达在炎症细胞 (中性粒细胞,巨细胞,巨细胞),而不是瘤细胞.
- 血液形成的MMP-9表达足以驱动MMP-9依赖的癌症发生.
结论:
- MMP-9在皮肤致癌过程中起着双重作用,促进了增殖,但也可能限制瘤的攻击性.
- 通过MMP-9的产生,炎症细胞作为状细胞致癌的关键贡献者.
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