Evidence for characteristic vascular patterns in solid tumours: quantitative studies using corrosion casts

Abstract

The vascular system plays a role of key importance during tumour growth and metastasis formation. In addition, the effectiveness of almost all therapeutic modalities, including drug therapy and radiotherapy, is influenced by the micro-architecture and the gradients of essential nutrients around each vessel. This underlines the importance of the vascular architecture, its origin and effectiveness as a nutrient delivery system. The knowledge that tumour vasculature is abnormal has led to concepts such as angiogenic attack and vascular targeting (Folkman, 1976;Denekamp, 1984;Bicknell, 1994;Folkman and D'Amore, 1996). This, in turn, has led to many more studies of tumour vasculature and primary as well as secondary angiogenesis. However, even though our knowledge of the mechanisms underlying angiogenesis has increased dramatically in the past 25 years, few quantitative data are available on the vascular network architecture and pattern formation in tumours.The fact that the tumour vascularity differs in many aspects from the vasculature of normal organs and tissues was already recognized in the last century (Virchow, 1863; Thiersch, 1865). Thomlinson and Gray (1955) indicated the importance of intervessel spacing because of the threefold increase in radioresistance that accompanies reduction of pO 2 concentrations below critical level. The important question as to whether the vascular architecture of an individual tumour is tumour type-specific has been controversial (Warren, 1979;Vaupel and Gabbert, 1986.) This is due, at least in part, to the methodologies used. Most reports confine themselves to qualitative observations and comparisons of gross vascular patterns in host and tumour, or to blood vessel density, length and diameter measurements, which in turn vary with the staining and counting techniques (Davidson et al, 1994;Endrich and Vaupel, 1998). Recently, morphometric analyses have been introduced in which the features of tumour cells (proliferation rate, oxygenation, angiogenic growth factor production) have been mapped by sequential staining of the same section, allowing the influence of the vascular assay on clinically relevant aspects of cell populations to be mapped. Vascular and metabolic profiles (VAMP) have illustrated marked differences between different types of tumour of the same general histology, for brain tumours and those from the head and neck region. Less et al (1991) introduced the first suitable approach for determining branching patterns and vessel dimensions in corrosion casts of mammary carcinomas. They established a quantitative classification scheme which takes account of the unique features of tumour microvascular network topology. However, it should be recognized that measurements were made on planar twodimensional (2D) projected images of three-dimensional (3D) specimens. All attempts to determine distances in corrosion casts geometrically after 2D projection inevitably include a considerable error. Measurements of vascular parameters such as intercapillary distance and vessel se...

Angiogenesis and vascular network of teratocarcinoma from embryonic stem cell transplant into seminiferous tubules

“…Earlier corrosion casting works have shown that branching angles and interbranching distances are specific and characteristic for each tissue including tumours (Konerding et al, , 1999. In our case, the vascular branching and bifurcation capillary pattern of the normal testis totally disappeared and the examined specimens exhibited features similar to an immature vascular network with heterogeneous vessel densities, frequent blindending, resin extravasations and vascular compressions (Jain, Angiogenesis of an experimental teratocarcinoma U Silván et al 1988).…”

3D microvascular architecture of pre-cancerous lesions and invasive carcinomas of the colon

“…Using this method we have recently demonstrated tumour typespecific vascular architectures in xenografted murine and human tumours (Konerding et al, 1999). Furthermore, the vascular architecture of an experimental tumour does not depend on the size and/or the rate of growth of the lesion but rather on features characteristic of the tumour cell type.…”

“…The casting specimens were prepared for scanning electron microscopy as described in detail earlier (Konerding et al, 1999). From all specimens between 10 and 25 stereo pairs of peripheral and central areas were recorded as stereo images using a tilt angle of 6˚.…”

“…We have recently shown that xenografts from different murine and human tumour cell lines display significant differences in their microvascular architecture in terms of tumour type-specific intervascular distances, interbranching distances, as well as vascular diameters (Konerding et al, 1999). This inherent tumour architecture is widely retained even under the influence of highly angiogenic and/or tumourigenic factors such as FGF-II (Konerding et al, 1998).…”

The use of the orthotopic model to validate antivascular therapies for cancer

“…These features contribute to a high intrinsic vascular permeability of macromolecules into the vasculature (Dvorak, 1991;Jain, 1987) and the consequent development of high interstitial fluid pressure (Boucher, 1990), which is augmented by inadequate lymphatic drainage. Tumour vascular networks are chaotic, featuring complex branching patterns and lack of hierarchy (Gillies, 1999;Konerding, 1999;Less, 1991). Vessel diameters are irregular and lengths between branching points are often very long.…”