Characterisation of the Vasculature Within a Murine Adenocarcinoma Growing in Different Sites to Evaluate the Potential of Vascular Therapies

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Abstract
Numerous vaso-active agents can affect vasculature in experimental solid tumours growing subcutaneously (s.c.), but these models are unlikely to reflect the vasculature of metastatic disease in man. The present study describes a murine orthotopic colon tumour which metastasises to the liver. Morphology and vascular pattern of caecal tumours is similar to s.c. tumours. Vascular occlusion caused by intravenous (i.v.) noradrenaline (NA) (160 μgkg−1) and hydralazine (HDZ) (10 mgkg−1) was 32% and 59% respectively for the caecal tumours compared with 35% and 78% for s.c. tumours. Significant morphological differences were seen between liver metastases and systemic deposits produced by i.v. inoculation of tumour cells. Liver metastases following orthotopic transplantation contained functional vasculature but no significant occlusion was seen with NA or HDZ. The vascular development and morphological appearance of secondary disease resulting from orthotopic implantation suggests that this would be a useful model for the study of agents that act either by vascular or anti-angiogenic mechanism.