Morphological analysis of the mechanisms of organ-specific metastasis using intravital multiphoton microscopy

我们可视化了肿瘤微环境中癌细胞和间质细胞之间的相互作用，包括器官特异性转移，以及使用活体TPLSM对转移性肿瘤异种移植瘤的实时化疗反应。脾内注射癌细胞后，癌细胞滞留在肝窦内。观察到癌细胞周围的血小板聚集，表明肿瘤细胞诱导的血小板聚集(TCIPA)现象。癌细胞从肝窦渗出至Disse间隙。观察到库普弗细胞围绕癌细胞的突起，表明库普弗细胞似乎吞噬了癌细胞。5-氟尿嘧啶(5-FU)或伊立替康化疗后，肿瘤细胞碎裂、凝聚、肿胀、细胞内空泡形成。结直肠癌肝转移瘤内可见血小板聚集，肿瘤血管内血流相对减少。脾内注射癌细胞前给予5-FU对癌细胞与肝窦内皮细胞的黏附无影响。由于皮下肿瘤生长速度快于肝转移瘤，我们没有建立荷瘤小鼠的肝转移模型。

We visualized the interactions between cancer cells and stromal cells in tumor microenvironment with regard to ‘organ-specific metastasis, and in vivo real-time chemotherapy response for metastatic tumor xenografts using intravital TPLSM. Cancer cells were arrested within hepatic sinusoids after intrasplenic cancer cell injection. Platelet aggregation surrounding a cancer cell was observed, indicating a phenomenon of tumor-cell induced platelet aggregation (TCIPA). Cancer cells were extravasated from hepatic sinusoids to the space of Disse. Protrusions of Kupffer cells surrounding a cancer cell were observed, indicating that Kupffer cells appear to phagocytose cancer cells. After 5-fluorouracil (5-FU) or irinotecan chemotherapy, tumor cell fragmentation, condensation, swelling and intracellular vacuoles were observed. The platelet aggregation and the relatively decreased blood flow in the tumor vessels of colorectal liver metastases were also observed. 5-FU administration prior to the intrasplenic injection of cancer cells didn’t influence the adhesion of cancer cells to endothelial cells of hepatic sinusoids. We didn’t establish a liver metastasis model in subcutaneous tumor bearing mice because of the faster growth of subcutaneous tumor than liver metastatic tumor.