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Microvessel diameters of human colon adenocarcinoma during acute treatment with serotonin
Abstract:
Modulation of tumor blood flow could be of clinical importance, especially when it is combined with radio- or chemotherapy. Serotonin (5-HT), a naturally occurring agent, selectively reduces tumor blood flow and consecutively inhibits the growth of many animal tumors. Therefore, we introduce a new preparation that allows the study of topically applied 5-HT (10(-8) to 10(-2) mol/l) in the microcirculation of a human colon adenocarcinoma. This tumor has been xenotransplanted subcutaneously under the dorsal surface of the ear in athymic nude mice. 5-HT was also tested in the normal skin. The microvascular diameters of large and small arterioles (A1-3) and venules (V1-4) as well as capillaries were measured via closed-circuit videomicroscopy. Normal skin arterioles and venules constricted at higher doses (> 10(-7) mol/l) of 5-HT. In human colon carcinoma, doses of 5-HT higher than 10(-7) mol/l caused constriction of these microvessels; yet, tumor arterioles constricted more than skin arterioles. Thus, 5-HT could selectively reduce blood flow of human colon adenocarcinoma. Based on these findings, we suggest that 5-HT can inhibit growth of human tumors by selectively constricting tumor arterioles.
Insights
Serotonin (5-HT) selectively constricts blood vessels in human colon adenocarcinoma xenografts. This agent shows potential for inhibiting tumor growth, especially when combined with other cancer therapies.
Area of Science:
- Oncology
- Pharmacology
- Vascular Biology
Background:
- Modulating tumor blood flow is crucial for enhancing radio- and chemotherapy efficacy.
- Serotonin (5-HT), a naturally occurring agent, has demonstrated selective reduction of tumor blood flow and inhibition of animal tumor growth.
Purpose of the Study:
- To investigate the effects of topically applied serotonin (5-HT) on the microcirculation of human colon adenocarcinoma xenografts.
- To compare the vascular response of tumor microvessels to 5-HT with that of normal skin microvessels.
Main Methods:
- Human colon adenocarcinoma xenotransplanted into athymic nude mice.
- Topical application of varying doses of serotonin (5-HT) (10^-8 to 10^-2 mol/l) to the tumor and normal skin.
- Measurement of microvascular diameters (arterioles A1-3, venules V1-4, capillaries) using closed-circuit videomicroscopy.
Main Results:
- Serotonin (5-HT) caused constriction of arterioles and venules in normal skin at doses > 10^-7 mol/l.
- In human colon carcinoma, 5-HT doses > 10^-7 mol/l induced microvessel constriction.
- Tumor arterioles exhibited greater constriction in response to 5-HT compared to skin arterioles, indicating selective action.
Conclusions:
- Serotonin (5-HT) selectively reduces blood flow in human colon adenocarcinoma.
- The selective vasoconstrictive effect of 5-HT on tumor arterioles suggests its potential as an agent to inhibit human tumor growth, possibly in conjunction with other therapies.