Papoutsi M, Sleeman J P, Wilting J
Anatomisches Institut der Albert-Ludwigs-Universität, D-79104 Freiburg i. Br., Germany.
Microsc Res Tech. 2001 Oct 15;55(2):100-7. doi: 10.1002/jemt.1161.
It has generally been assumed that tumors do not induce lymphangiogenesis and only very recently animal models have been presented showing tumor-induced lymphangiogenesis. We have grown two types of rat tumor cells, 10AS pancreatic carcinoma and C6 glioma cells, on the chorioallantoic membrane (CAM) of chick and quail embryos. The suspended tumor cells rapidly formed solid tumors which invaded the CAM and were vascularized by CAM vessels. When grown on the CAM of quail embryos intratumoral endothelial cells could be specifically stained with the QH1 antibody. In C6 gliomas the vascular pattern was more regular than in 10AS carcinomas. The vessels often grew radially into the glioma and many of them were invested by smooth muscle alpha-actin-positive periendothelial cells. Lymphatics, which were identified by vascular endothelial growth factor receptor-3 (VEGFR-3) in situ hybridization were absent from C6 gliomas, although a weak expression of the lymphangiogenic growth factor, VEGF-C, could be detected in the C6 cells by Northern blot analysis. In contrast, 10AS cells, which expressed high levels of VEGF-C, induced ingrowth of lymphatics into the tumors, with BrdU-labeling rates of about 9% of lymphatic endothelial cells. Our studies demonstrate the heterogeneity of interactions of tumor cells with blood vessels and lymphatics and show that sufficient quantities and/or quality of lymphangiogenic growth factors are crucial for the induction of lymphatics in tumors.
一般认为肿瘤不会诱导淋巴管生成，直到最近才有动物模型显示肿瘤可诱导淋巴管生成。我们将两种大鼠肿瘤细胞，即10AS胰腺癌细胞和C6胶质瘤细胞，接种于鸡胚和鹌鹑胚的绒毛尿囊膜（CAM）上。悬浮的肿瘤细胞迅速形成实体瘤，侵袭CAM并由CAM血管形成血管化。当在鹌鹑胚的CAM上生长时，肿瘤内的内皮细胞可用QH1抗体进行特异性染色。在C6胶质瘤中，血管模式比10AS癌更规则。血管常呈放射状长入胶质瘤，其中许多被平滑肌α-肌动蛋白阳性的血管周细胞包绕。通过血管内皮生长因子受体-3（VEGFR-3）原位杂交鉴定的淋巴管在C6胶质瘤中不存在，尽管通过Northern印迹分析在C6细胞中可检测到淋巴管生成生长因子VEGF-C的弱表达。相反，表达高水平VEGF-C的10AS细胞可诱导淋巴管长入肿瘤，淋巴管内皮细胞的BrdU标记率约为9%。我们的研究证明了肿瘤细胞与血管和淋巴管相互作用的异质性，并表明足够数量和/或质量的淋巴管生成生长因子对于肿瘤中淋巴管的诱导至关重要。
