Three-dimensional analysis of tumour vascular corrosion casts using stereoimaging and micro-computed tomography

Abstract

Objective: In order to perform effective translational research for cancer therapy, we need to employ pre-clinical models which reflect the clinical situation. The purpose of this study was to quantitatively compare the vascular architecture of human colorectal cancer and experimental tumour models to determine the suitability of animal models for vascular studies and antivascular therapy.

Methods: In this study we investigated the three-dimensional properties of colonic tumour vasculature in both human clinical tissues (normal mucosa control [n=20], carcinoma [n=20] and adenoma [n=6]) and murine colorectal xenografts (LS147T [n=6] and SW1222 [n=6]). Scanning Electron Microscope Stereoimaging (SEM) and X-ray Micro-Computed Tomography (Micro-CT) methods were employed for 3D analyses of the vascular corrosion casts from these tissues.

Results: Morphological measurements showed that there were significant differences in the underlying morphology in the different tissues. Of the studied xenografts, LS147T is more consistently similar to the vascular architecture of the human carcinoma than SW1222. The only reversal of this is for the inter-vessel distance.

Conclusion: While SEM stereoimaging provided better surface detailed resolution of the corrosion casts, it was complimented by the fully 3D micro-CT method. Comparison made between the xenografts and clinical tumours showed that the LS147T xenografts shared many similarities with the clinical tumour vasculature. This study provides insight into how to select the most suitable pre-clinical models for translational studies of clinical cancer therapy.

Fig. 1

Xenograft histology

Fig. 2

SEM micrographs of clinical casts

Fig. 2

SEM micrographs of clinical casts

Fig. 3

SEM micrographs of xenograft casts

Fig. 4

Distributions of SEM measurements

Fig. 5

Micro-CT volume rendering of tumour vascular casts

Fig. 5

Micro-CT volume rendering of tumour vascular casts

Fig. 6

Distributions of micro-CT measurements