Abstract
The intratumoral microvessel density of malignant breast cancer has been shown to be an important prognostic marker. In this study, we tested whether repeated treatment with hyperthermia and serotonin (5-hydroxytryptamine) reduces tumor growth and alters tumor histology of a colon adenocarcinoma, and whether capillary density in this tumor can also be regarded as an important prognostic marker. Previously we have shown that acute treatment of colon adenocarcinoma with hyperthermia, alone or in combination with serotonin, selectively constricted tumor microvessels, which could reduce blood flow and inhibit tumor growth. Fourteen days after human colon adenocarcinoma had been transplanted under the dorsal epidermis of the ear of athymic nude mice, the surgically unprepared tumor-bearing ear of the sodium-pentobarbital-anesthetized animal was treated with hyperthermia alone (group 1, 43°C for 45 min), or with hyperthermia plus topically applied serotonin (1 mM/l, 43°C for 45 min, group 2) twice per week for 5 weeks. Control animals were not treated (group 3). Histological slides (stained with hematoxylin/eosin) were prepared 42 days after implantation, for analysis of tumor grading, tumor cell invasion into the surrounding tissue and microvessels, and the number of intratumoral microvessels. Repeated hyperthermia inhibited tumor growth, reduced the number of intratumoral microvessels, did not change tumor cell invasion and increased the necrotic area. Hyperthermia and serotonin did not influence tumor growth, but strongly reduced cell invasion and the number of microvessels. The area of necrosis was very large. Thus, analysis of microvessel density in colon adenocarcinoma seems not to be an important tool for predicting therapeutic efficacy.
Similar content being viewed by others
References
Burtin C, Scheinmann P, Salomon JC (1982) Decrease in tumour growth by injections of histamine and serotonin in fibrosarcoma-bearing mice: influence of H1 and H2 histamine receptors. Br J Cancer 45: 54–60
Cater DB, Grigson CMB, Watkinson DA (1962) Changes in oxygen tension in tumours induced by vasoconstrictor and vasodilator drugs. Acta Radiol 58: 401–434
Crile G (1963) The effects of heat and radiation on cancers implanted on the feet of mice. Cancer Res 23: 372–380
Dickson JA, Shah SA (1982) Hyperthermia: the immune response and tumor metastasis. Natl Cancer Inst Monogr 61: 183–192
Folkman J (1990) What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 82: 4–6
Giovanella BC, Stehlin JS, Shepard RC (1979) Hyperthermic treatment of human tumors heterotransplanted in nude mice. Cancer Res 39: 2236–2241
Huhnt W, Lübbe AS (1995) Venules and arterioles in xenotransplanted human colon adenocarcinoma critically constrict with hyperthermia and serotonin. J Cancer Res Clin Oncol 121: 267–274
Jain RK (1994) Barriers to drug delivery in solid tumors. Sci Am 270: 42–49
Liotta L, Kleinerman J, Saidel G (1974) Quantitative relationships of intravascular tumor cells, tumor vessels, and pulmonary metastases following tumor implantation. Cancer Res 34: 997–1004
Lübbe AS, Huhnt W (1994) Microvessel diameters of human colon adenocarcinoma during acute treatment with serotonin. Int J Microcirc 14: 218–225
NIH (1978) Guide for the care and use of laboratory animals. DHEW publication, (NIH) 80-22. Office of Science and Health Reports, DRR/NIH, Bethesda, Md
Orvoine RH (1981) Influence of various hexoses and vasoactive agents on osmotically induced oncolysis. Cancer Res 37: 102–105
Shrivastav S, Joines WT, Jirtle RL (1985) Effect of 5-hydroxytryptamine on tissue blood flow and microwave heating of rat tumors. Cancer Res 45: 3203–3208
Song CW, Rhee JG, Levitt SH (1980) Blood flow in normal tissues and tumors during hyperthermia. J Natl Cancer Inst 64: 119–124
Srivastava A, Laidler P, Davies RP, Horgan K, Hughes LE (1988) The prognostic significance of tumor vascularity in intermediate-thickness (0.76–4.0 mm thick) skin melanoma: a quantitative histologic study. Am J Pathol 133: 419–423
Urano M, Kahn J (1985) Effect of 42°C hyperthermia on murine normal and tumor tissues. Cancer Res 45: 2527–2532
Vaupel P, Kallinowski F, Kluge M, Engelhof E, Fortmeyer HP (1987) Microcirculatory and pH alterations in isotransplanted rat and xenotransplanted human tumors associated with hyperthermia. Recent Results Cancer Res 109: 174–182
Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis-correlation in invasive breast cancer. N Engl J Med 324: 1–8
Author information
Authors and Affiliations
Additional information
This work was sponsored by the Deutsche Krebshilfe and Deutsche Krebsgesellschaft
Rights and permissions
About this article
Cite this article
Huhnt, W., Lübbe, A.S. Growth, microvessel density and tumor cell invasion of human colon adenocarcinoma under repeated treatment with hyperthermia and serotonin. J Cancer Res Clin Oncol 121, 423–428 (1995). https://doi.org/10.1007/BF01212950
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01212950