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Abstract
The effects of tumour cells (Colon 26) on the development and response of new blood vessels to different vasoconstrictors (platelet activating factor; PAF, endothelin-1, angiotensin II, adrenalin and 5-hydroxytryptamine) have been investigated. Sponge implants in mice were used to host tumour cells while washout of 133Xe was employed to assess local blood flow in the implanted sponges. By 14 days after implantation the response of vessels in tumour-bearing implants to the various vasoconstrictors generally was decreased compared to that obtained in control sponge implants or adjacent normal skin. Thus at this time point the t1/2 for 133Xe washout from control sponges treated with adrenalin (0.5 micrograms) was 30 +/- 4 min whereas in tumour-bearing sponges it was 5 +/- 1 min. This decreased sensitivity in tumour vessels was probably not due to a complete lack of contractile elements since actin was demonstrated by immunohistochemistry around blood vessels in both types of implant. The results of the present study have shown that the pharmacological responses of blood vessels in a growing tumour, Colon 26, differed from the responses of vessels of a similar age in non-neoplastic tissue. These results appear to suggest that the different angiogenic stimuli released from tumour tissue may markedly influence pharmacological reactivity of newly formed blood vessels.
Highlights
By 14 days after implantation the response of vessels in tumour-bearing implants to the various vasoconstrictors generally was decreased compared to that obtained in control sponge implants or adjacent normal skin
The results of the present study have shown that the pharmacological responses of blood vessels in a growing tumour, Colon 26, differed from the responses of vessels of a similar age in non-neoplastic tissue. These results appear to suggest that the different angiogenic stimuli released from tumour tissue may markedly influence pharmacological reactivity of newly formed blood vessels
In this paper, using our sponge implant system to host Colon 26 tumours and washout of '33Xe to assess local blood flow in the implanted sponges, we have studied the angiogenic effects of an adenocarcinoma on neovascularisation of sponge implants in Balb/c mice and on the pharmacological responses of the newly formed vessels
Summary
Polyether-polyurethane sponge discs, 4 mm height x 8 mm diameter (Vitafoam Ltd., Manchester, UK) were used as the matrix to host tumour cells and to monitor for angiogenesis. The sponge discs with cannula attached were soaked overnight in 70% v/v ethanol and sterilised by boiling in distilled water for 15 min. Discs were implanted using aseptic techniques in mice anaesthetised by intramuscular injection of Hypnorm and Hypnovel (0.5 ml kg-' of each). A sterilised sponge implant was inserted in the pocket, its cannula being pushed through a small incision which had been made previously on the top of the pocket. The base of the cannula was sutured to the skin. The mid-line incision was closed by 2-3 silk sutures and the animals were housed singly with free access to food and water
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