The vascular architecture of human xenotransplanted tumors: histological, morphometrical, and ultrastructural studies

Abstract

This study was designed to examine the vascular system of human xenotransplanted tumors on nude mice with different complementary morphometrical and morphological methods. The vascular system shows a chaotic arrangement. There is an extreme heterogeneity in the vascular distribution and density. Large avascular regions could be identified in several non-necrotic tumors. There was no clear difference in the vascular density between the center and the periphery of the tumors, nor was there any zonal correlation for the distribution of the necrosis. With three-dimensional corrosion casts it could be demonstrated that clusters of vessels were directly beneath areas almost free of vessels. In the center, vessels often form a sinusoidal system with numerous blind ends without clearly discernible endothelial cells. Numerous irregular tumor-cell-lined sinusoids are visible next to endothelial-lined vessels with transmission electron microscopy. With scanning electron microscopy it could be demonstrated that large-calibre endotheliazed vessels were found in the direct vicinity or in the center of non-viable zones. Even large-calibre vessels have a capillary wall structure. Sometimes, a basement membrane cannot be observed at all or only incompletely. There are numerous indications of vascular discontinuities and leaks with a widespread intercellular occurrence of blood cells.

Endothelin-1 and Angiogenesis in Cancer

“…They have a paucity of pericytes and vascular smooth muscle cells (VSMC) around the vessels; often endothelial cells and tumour cells are separated by only an incomplete basement membrane [5][6][7]. In some tumours, eg breast, colon and melanoma the endothelial layer is incomplete and a mosaic of tumour cells and endothelial cells forms the vessel lining [4,8,9]. About 15% of the tumour vessel lining in colonic cancers is made up of tumour cells [10].…”

Analysis of Effective Molecular Diffusion Rates for Verteporfin in Subcutaneous Versus Orthotopic Dunning Prostate Tumors¶

“…Tumor vessels have irregular structures, diameters and branching patterns (1)(2)(3)(4), as well as thin walls, and an incomplete basement membrane and abnormal pericytes (5)(6)(7)(8). These anatomic abnormalities are likely the origin of the unusual leakiness, intermittent blood flow, low pressure, spontaneous hemorrhage and stasis, which are all observed in local regions of the tumor (9)(10)(11)(12)(13)(14).…”

Openings between Defective Endothelial Cells Explain Tumor Vessel Leakiness

“…In addition, some vessels have an incomplete basement membrane and an abnormal pericyte coat. [5][6][7][8] Other abnormalities include unusually avid binding and uptake of cationic liposomes, and expression of integrins, growth factors, and receptors that differ from those of normal vessels. 9 -14 Of particular functional importance, tumor vessels are unusually leaky.…”