Organ-specific metastatic tumor cell adhesion and extravasation of colon carcinoma cells with different metastatic potential

Organ-specific metastatic tumor cell adhesion and extravasation of colon carcinoma cells with different metastatic potential
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DOI:
10.2353/ajpath.2006.050566
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发表时间:
2006-09-01
影响因子:
6
通讯作者:
Haier, Joerg
Haier, Joerg
中科院分区:
医学2区
文献类型:
--
作者:
Schlueter, Kerstin;Gassmann, Peter;Haier, Joerg

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粘附性和侵袭性特征对于器官特异性转移的形成似乎是至关重要的。使用活体显微镜,我们研究了结肠癌细胞的转移潜力和它们的粘附和侵袭行为之间的关系,在大鼠肝,肺,肠,皮肤,肌肉,脾和肾在体内的微血管内转移的早期步骤。将具有低(HT-29 P)、中等(KM-12 C)和高(HT-29 LMM、KM-12 L4)转移潜能的结肠癌细胞注射到裸大鼠或Sprague-Dawley大鼠中。在20至30分钟内半定量分析与宿主器官微血管的初始相互作用。循环细胞通过所有观察器官中的微血管,无大小限制。所有细胞系在肝和肺内显示出高粘附率,与其转移潜力无关,但在其他器官中很少。受累微血管直径大于贴壁肿瘤细胞直径。高转移HT-29 LMM和KM-12 L4细胞向肝实质内的外渗率显著高于低转移细胞(P < 0.05)。我们的研究结果表明,结肠癌细胞可以在靶器官中停滞而不受大小限制。循环肿瘤细胞的细胞粘附仅发生在转移性靶器官中,可能归因于特异性相互作用。向靶器官的迁移与其转移潜力相关。
Adhesive and invasive characteristics appear to be crucial for organ-specific metastasis formation. Using intravital microscopy we investigated the relation between the metastatic potential of colon carcinoma cells and their adhesive and invasive behavior during early steps of metastasis within microvasculatures of rat liver, lung, intestine, skin, muscle, spleen, and kidney in vivo. Colon carcinoma cells with low (HT29P), intermediate (KM-12C), and high (HT-29LMM, KM-12L4) metastatic potential were injected into nude or Sprague-Dawley rats. Initial interactions with host organ microvasculatures were semiquantitatively analyzed throughout 20 to 30 minutes. Circulating cells passed microvessels in all observed organs without size restriction. All cell lines showed high adhesion rates, independent from their metastatic potential, within liver and lung but very rarely in other organs. Diameters of involved microvessels were larger than diameters of adherent tumor cells. Cell extravasation of highly metastatic HT-29LMM and KM-12L4 cells into liver parenchyma was significantly higher compared to low metastatic cells (P < 0.05). Our results indicate that colon carcinoma cells can arrest in target organs without size restriction. Cell adhesion of circulating tumor cells occurred in metastatic target organs only, likely attributable to specific interactions. Migration into target organs correlated with their metastatic potential.