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Comparative Morphometric Study of Tumor Vasculature in Human Squamous Cell Carcinomas and Their Xenotransplants in Athymic Nude Mice¹

Department of Radiation Medicine, Massachusetts General Hospital [S. L., A. Z., S. S., H. D. S.]; and the Massachusetts Eye and Ear Infirmary, Harvard Medical School [R. F.]; Boston, Massachusetts 02114

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 antifactor 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 µm to 99 µm and 53 µm to 65 µm, 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 rarefication 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.

¹ This work was supported in part by DHHS Grant CA-13311 and DFG Grant La-576/1-1.

² To whom requests for reprints should be addressed, at Institut für Strahlenbiologie, Gesellschaft für Strahlen-und Umweltforschung, D 8042 Neuherberg, FRG.

Received 11/ 4/88. Revised 3/ 3/89. Revised 5/ 3/89. Accepted 5/15/89.

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