Rupertus Kathrin, Kollmar Otto, Scheuer Claudia, Junker Bastian, Menger Michael D, Schilling Martin K
Department of General, Visceral, Vascular and Pediatric Surgery, University of Saarland, 66421 Homburg/Saar, Germany.
Clin Exp Metastasis. 2007;24(1):39-48. doi: 10.1007/s10585-006-9054-6. Epub 2007 Jan 27.
The effect of hepatectomy and hepatic regeneration on intra- and extrahepatic tumor growth is still controversially discussed. Herein we studied the effect of minor (30%) or major (70%) hepatectomy on engraftment of extrahepatic tumor cells, and the role of tumor neovascularization and tumor cell migration.
Green fluorescent protein (GFP)-transfected CT26.WT colorectal cancer cells were implanted in dorsal skinfold chambers of syngeneic BALB/c mice. Animals underwent 30% (30%Phx, n = 8) or 70% hepatectomy (70%Phx, n = 8). Sham-operated animals served as controls (n = 8). Angiogenesis and neovascularization as well as tumor cell migration, proliferation and growth were studied over 14 days using intravital fluorescence microscopy, histology and immunohistochemistry.
After both minor and major hepatectomy tumor proliferating cell nuclear antigen (PCNA) expression increased significantly (P < 0.05) when compared with nonhepatectomized controls. However, only major but not minor hepatectomy accelerated neovascularization (P < 0.05) and tumor cell migration (P < 0.05). This was associated with a significantly (P < 0.05) enhanced tumor growth after 70%Phx when compared with 30%Phx and controls. The rate of apoptotic cell death was not affected by major or minor hepatectomy.
Regeneration after major hepatectomy accelerates extrahepatic tumor cell engraftment, most probably by acceleration of neovascularization and induction of tumor cell migration.
肝切除术及肝再生对肝内和肝外肿瘤生长的影响仍存在争议。在此,我们研究了小范围(30%)或大范围(70%)肝切除术对肝外肿瘤细胞植入的影响,以及肿瘤新生血管形成和肿瘤细胞迁移的作用。
将绿色荧光蛋白(GFP)转染的CT26.WT结肠癌细胞植入同基因BALB/c小鼠的背部皮褶小室中。动物接受30%(30%肝切除组,n = 8)或70%肝切除术(70%肝切除组,n = 8)。假手术动物作为对照(n = 8)。使用活体荧光显微镜、组织学和免疫组织化学方法,在14天内研究血管生成和新生血管形成以及肿瘤细胞迁移、增殖和生长情况。
与未进行肝切除的对照组相比,小范围和大范围肝切除术后肿瘤增殖细胞核抗原(PCNA)表达均显著增加(P < 0.05)。然而,只有大范围而非小范围肝切除术加速了新生血管形成(P < 0.05)和肿瘤细胞迁移(P < 0.05)。这与70%肝切除组相比30%肝切除组和对照组,肿瘤生长显著增强(P < 0.05)相关。细胞凋亡率不受大范围或小范围肝切除术的影响。
大范围肝切除术后的肝再生加速了肝外肿瘤细胞的植入,很可能是通过加速新生血管形成和诱导肿瘤细胞迁移实现的。