Lauk S, Zietman A, Skates S, Fabian R, Suit H D
Department of Radiation Medicine, Massachusetts General Hospital, Boston.
Cancer Res. 1989 Aug 15;49(16):4557-61.
When human tumor xenotransplants into nude mice are used as experimental models, it is important to know whether their microvascular anatomy is rather host or tumor specific. Therefore a morphometric comparison of the vascular network in human squamous cell carcinomas and their xenotransplants was carried out. Biopsies were taken from surgical specimens of three squamous cell carcinomas of the oral cavity. Part of the material was processed for histology and the rest was cut into 1-mm3 cubes and transplanted s.c. into the lateral thorax of athymic nude mice [NCr/Sed(nu/nu)]. The microvascular architecture of original tumors and of three first, one second, and one late generation xenografts was compared. Capillaries were identified in original human tumors by anti-factor VIII staining and in xenografts with antilaminin staining. The median distances between interphase tumor cells and blood vessels were determined and were found to be much longer in original human tumors than in xenografts, ranging from 81 microns to 99 microns and 53 microns to 65 microns, respectively. However, the characteristic qualitative histology of tumors appeared to be preserved in xenotransplants. Analysis of the topographic distribution of mitotic figures revealed that in both original tumors and xenotransplants proliferation of tumor cells was concentrated around blood vessels. Again, vascular distances in original tumors were significantly longer than in xenotransplants. In addition, xenotransplants into nude mice from a long passaged cell line from a human pharyngeal squamous cell carcinoma, FaDu, was investigated. FaDu showed a rare-fication of the capillary network with increasing tumor volume, but a constant median distance of mitotic figures from blood vessels. In conclusion, the pattern of spatial distribution of proliferating tumor cells as well as differentiation characteristics appear to be retained in xenograft tumors, but the density of the vascular system is host specific. This has to be taken into account when physiological parameters of blood supply are studied in xenotransplanted tumors.
当将人类肿瘤异种移植到裸鼠体内用作实验模型时，了解其微血管解剖结构是更具宿主特异性还是肿瘤特异性非常重要。因此，对人类鳞状细胞癌及其异种移植中的血管网络进行了形态计量学比较。从口腔的三例鳞状细胞癌手术标本中获取活检组织。部分材料用于组织学处理，其余切成1立方毫米的小块，皮下移植到无胸腺裸鼠[NCr/Sed(nu/nu)]的侧胸。比较了原发肿瘤以及第1代、第2代和第3代异种移植瘤的微血管结构。通过抗VIII因子染色在原发人类肿瘤中识别毛细血管，通过抗层粘连蛋白染色在异种移植瘤中识别毛细血管。测定了相间肿瘤细胞与血管之间的中位距离，发现原发人类肿瘤中的距离比异种移植瘤中的长得多，分别为81微米至99微米和53微米至65微米。然而，肿瘤的特征性定性组织学在异种移植中似乎得以保留。对有丝分裂象的地形分布分析表明，在原发肿瘤和异种移植瘤中，肿瘤细胞的增殖都集中在血管周围。同样，原发肿瘤中的血管距离明显长于异种移植瘤。此外，还研究了将来自人咽鳞状细胞癌的长期传代细胞系FaDu异种移植到裸鼠体内的情况。FaDu显示随着肿瘤体积的增加，毛细血管网络变得稀疏，但有丝分裂象与血管的中位距离保持不变。总之，增殖性肿瘤细胞的空间分布模式以及分化特征在异种移植瘤中似乎得以保留，但血管系统的密度具有宿主特异性。在研究异种移植瘤的血液供应生理参数时必须考虑到这一点。
