线形程序性坏死在不同肿瘤局部微环境中分布的初步观察

The Pilot Study on Linearly Patterned Programmed Cell Necrosis and Local Tumor Microenvironments

目的:观察肿瘤局部微环境对肿瘤细胞发生线形程序性坏死(LPPCN)的影响。方法:C57BL小鼠9只,结扎小鼠左后肢股动脉,注射B16单细胞悬液于左后肢(缺血组)和右后肢(对照组),构建B16F10小鼠黑色素瘤后肢缺血模型;C57BL小鼠10只,注射B16单细胞悬液于小鼠腹腔(腹腔组)和左后肢(后肢组),构建小鼠黑色素瘤生物力学模型;HE切片观察不同组间LPPCN分布的差别;免疫组织化学染色检测肿瘤组织基质金属蛋白酶(MMP)-2、MMP-9的表达。结果:LPPCN细胞百分率比较,缺血组高于对照组,后肢组高于腹腔组,差异均有统计学意义(均P<0.01);MMP-2、MMP-9阳性细胞百分率比较,缺血组高于对照组,后肢组高于腹腔组,差异均有统计学意义(均P<0.01)。结论:肿瘤局部缺氧和压力变化可以上调MMP-2、MMP-9的表达并诱导肿瘤细胞发生LPPCN。

Objective：To investigate the influence of the local tumor microenvironments on the linearly patterned programmed cell necrosis （LPPCN）. Methods：The left femoral arteries of 9 C57BL mice were ligated and then B16F10 melanoma cell suspension was injected into the left ischemic skeletal muscles and nonischemic right controls respectively to build the ischemic animal model. The biomechanical animal model was built by injecting the B16F10 melanoma cell suspension into the abdominal cavity and left skeletal muscles in 10 C57BL mice. HE staining was performed to compare the LPPCN distribution between groups. Immunohistochemistry was employed to detect the expression of matrix metalloproteinase-2 and 9 （MMP-2 and MMP-9）. Results：The numbers of LPPCN cells were significantly higher in ischemic group and skeletal muscle group than those in control group （P〈 0.01） and the abdominal cavity group （P〈 0.01）. Similarly,the expressions of MMP-2 and MMP-9 were significantly higher in ischemic group and the skeletal muscle group than those in control group （P 〈0.01）and the abdominal cavity group （P 〈0.01）. Conclusion：Hypoxia and microenvironment pressure of tumor can increase MMP-2 and MMP-9 expression and influence the LPPCN formation.