Metastatic tumor cell arrest in the liver-lumen occlusion and specific adhesion are not exclusive
Metastatic tumor cell arrest in the liver-lumen occlusion and specific adhesion are not exclusive
复制标题
DOI：
10.1007/s00384-009-0694-2
复制
发表时间：
2009-07-01
影响因子：
2.8
通讯作者：
Haier, Joerg
中科院分区：
文献类型：
--
作者：
Gassmann, Peter;Hemping-Bovenkerk, Andre;Haier, Joerg
在转移研究中，现代显微技术为转移性肿瘤细胞在潜在转移靶器官微循环中的阻滞机制提供了新的思路。在本研究中，我们区分了机械细胞阻滞的作用，确定为肿瘤细胞对肝窦腔的阻塞，以及整合素介导的特异性细胞粘附在大鼠肝脏中对人结肠癌细胞的阻滞。采用活体显微镜法测定两种不同大鼠品系（CD, 250 ~ 300 g， RNU, 80 ~ 120 g）肝窦直径。心内注射细胞（HT-29LMM），测定阻滞细胞数和窦状动脉闭塞细胞率。CD大鼠的平均正弦波直径为6.98 +/- 1.42 A μ m， RNU大鼠为5.14 A +/- 1.11 A μ m （p < 0.001）。两株大鼠的肿瘤细胞滞留数和肿瘤细胞外渗率无显著差异。然而，细胞注射后5和30 min， RNU大鼠分别有35 A +/- 15%和19 A +/- 8%的阻滞细胞出现腔隙闭塞，CD大鼠分别有9 A +/- 6%和3 A +/- 3%出现腔隙闭塞（p < 0.05）。尽管RNU大鼠的管腔闭塞细胞率较高，但抑制β -1或β -4整合素显著损害了这两种菌株中30-60%的细胞阻滞。综上所述，这些结果表明，通过体内显微镜检测，仅管腔闭塞不足以在转移靶器官中建立稳定的结肠癌肿瘤细胞阻滞，因此不排除在微循环中对肿瘤细胞阻滞的特异性粘附相互作用的要求。
In metastasis research, modern microscopic techniques shed a new light on the mechanisms of metastatic tumor cell arrest in the microcirculation of potential metastasis target organs. In this study, we differentiated the contribution of mechanical cell arrest, determined as lumen occlusion of liver sinusoids by tumor cells, and specific cell adhesion mediated by integrins for the arrest of human colon cancer cells in rat livers.Using in vivo microscopy, the diameters of liver sinusoids of two different rat strains (CD, 250-300 g and RNU, 80-120 g) were determined. Cells (HT-29LMM) were intracardially injected, and the numbers of arrested cells and the rates of sinusoid occluding cells were determined.Mean sinusoid diameter in CD rats was 6.98 +/- 1.42 A mu m compared to 5.14 A +/- 1.11 A mu m in RNU rats (p < 0.001). The numbers of arrested tumor cells and the rates of extravasated tumor cells did not differ between the two rat strains. Nevertheless, 5 and 30 min after cell injection, 35 A +/- 15% and 19 A +/- 8% of arrested cells, respectively, appeared lumen occluding in RNU rats and 9 A +/- 6% and 3 A +/- 3%, respectively, in CD rats (p < 0.05). Despite the higher rates of lumen occlusive cells in RNU rats, inhibition of beta-1 or beta-4 integrins significantly impaired cell arrest by 30-60% in both strains.In summary, these results demonstrate that lumen occlusion alone, as determined by in vivo microscopy, is insufficient to establish stable tumor cell arrest of colon carcinoma cells in metastatic target organs and does therefore not rule out the requirement of specific adhesive interactions for tumor cell arrest in the microcirculation.