Skip to main content
SpringerLink
Log in

The vascular architecture of human xenotransplanted tumors: histological, morphometrical, and ultrastructural studies

  • Original Papers
  • Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Summary

This study was designed to examine the vascular system of human xenotransplanted tumors on nude mice with different complementary morphometrical and morphological methods. The vascular system shows a chaotic arrangement. There is an extreme heterogeneity in the vascular distribution and density. Large avascular regions could be identified in several non-necrotic tumors. There was no clear difference in the vascular density between the center and the periphery of the tumors, nor was there any zonal correlation for the distribution of the necrosis. With three-dimensional corrosion casts it could be demonstrated that clusters of vessels were directly beneath areas almost free of vessels. In the center, vessels often form a sinusoidal system with numerous blind ends without clearly discernible endothelial cells. Numerous irregular tumor-cell-lined sinusoids are visible next to endothelial-lined vessels with transmission electron microscopy. With scanning electron microscopy it could be demonstrated that large-calibre endotheliazed vessels were found in the direct vicinity or in the center of non-viable zones. Even large-calibre vessels have a capillary wall structure. Sometimes, a basement membrane cannot be observed at all or only incompletely. There are numerous indications of vascular discontinuities and leaks with a widespread intercellular occurrence of blood cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Appelgren KL (1979) Methods of recording tumor blood flow. In: Peterson HI (eds) Tumor blood circulation, CRC Press, Boca Raton, Florida, pp 87–102

    Google Scholar 

  • Bastert G, Fortmeyer HP, Eichholz H, Michel RI, Huck R, Schmidt-Matthiesen H (1981) Human breast cancer in thymus aplastic nude mice. In: Bastert G, Fortmeyer HP, Schmidt-Matthiesen H (eds) Thymus aplastic nude mice and rats in clinical oncology. Fischer, Stuttgart, pp 157–182

    Google Scholar 

  • Budach V, Bamberg M, Donhuijsen K, Schmidt U, van Beuningen D, Stuschke M (1986) Serial xenotransplantation of a human embryonal carcinoma in experimental urology. J Urol 136:1143–1147

    Google Scholar 

  • Dalton AJ (1955) A chrome-osmium fixative for electron microscopy. Anat Rec 121:281–285

    Google Scholar 

  • Denekamp J (1984) Vascular endothelium as the vulnerable element in tumors. Acta Radiol Oncol 23:217–225

    Google Scholar 

  • Denekamp J (1987) Attacking tumour vasculature. (Proc 8th ICRR) Radiat Res 2:795–806

    Google Scholar 

  • Donhuijsen K, van Beuningen D, Budach V, Schmidt U (1988) Instability of xenotransplanted soft tissue sarcomas: morphologic and flow cytometric results. Cancer 61:68–75

    Google Scholar 

  • Endrich B (1988) Hyperthermie und Tumormikrozirkulation. Beitr Onkol 31:19–49

    Google Scholar 

  • Endrich B, Hammersen F, Götz A, Meßmer K (1982) Microcirculatory blood flow, capillary morphology, and local oxygen pressure of the hamster amelanotic melanoma A-Mel-3. J Natl Cancer Inst 68:474–485

    Google Scholar 

  • Frankl O, Kimball G (1914) Über die Beeinflussung von Mäusetumoren durch Roentgenstrahlen. Klin Wochenschr 27:1448–1450

    Google Scholar 

  • Gabbert H, Wagner R, Höhn P (1982) The relation between tumor cell proliferation and vascularisation in differentiated and undifferentiated colon carcinomas in the rat. Virchows Arch [B] 41:119–131

    Google Scholar 

  • Gassmann A (1899) Zur Histologie der Roentgenulcera. Fortschr Roentgenstr. 2: 199–207

    Google Scholar 

  • Grunt TW, Lametschwandtner A, Karrer K, Staindl O (1986a) The angioarchitecture of the Lewis lung carcinoma in laboratory mice. Scanning Electron Microsc 2:557–573

    Google Scholar 

  • Grunt TW, Lametschwandtner A, Karrer K (1986b) The characteristic structural features of the blood vessels of the Lewis lung carcinoma. Scanning Electron Microsc 2:575–589

    Google Scholar 

  • Hammersen F, Osterkamp-Baust U, Endrich B (1983) Ein Beitrag zum Feinbau terminaler Strombahnen und ihrer Entstehung in bösartigen Tumoren. In: Meßmer K, Hammersen F (eds) Mikrozirkulation in Forschung und Klinik. (Structure and function of endothelial cells, vol 1) Karger, Basel, pp 15–51

    Google Scholar 

  • Hirst DG, Denekamp J (1979) Tumour cell proliferation in relation to the vasculature. Cell Tissue Kinet 12:31–42

    Google Scholar 

  • Hodde KC, Nowell JA (1980) SEM of microcorrosion casts. Scanning Electron Microsc 2:88–106

    Google Scholar 

  • Illig L (1961) Die terminale Strombahn — Capillarbett und Mikrozirkulation. Springer, Berlin Göttingen Heidelberg, S 60–99

    Google Scholar 

  • Jain RK (1988) Determinants of tumor blood flow: review. Cancer Res 48:2641–2658

    Google Scholar 

  • Kallinowski F, Vaupel P, Runkel S, Berg G, Fortmeyer HP, Baessler KH, Wagner K, Mueller-Klieser W, Walenta S (1988) Glucose uptake, lactate release, ketone body turnover, metabolic micromilieu, and pH distribution in human breast cancer xenografts in nude rats. Cancer Res 48:7264–7272

    Google Scholar 

  • Konerding MA, Steinberg F (1988) Computerized infrared thermographic and ultrastructural studies of xenotransplanted human tumors on nude mice. Thermology 3:7–14

    Google Scholar 

  • Konerding MA, Steinberg F, Budach V (1989a) The vascular system of xenotransplanted tumors — scanning electron microscopic studies. Scanning Electron Microsc 3:327–336

    Google Scholar 

  • Konerding MA, Steinberg F, Streffer C (1989b) Ultrastructural studies on the vascular system of untreated and hyperthermia treated xenotransplanted tumors. Proc 5th Int Symp Hyperthermic Oncol 1:344–346

    Google Scholar 

  • Kraus W, Fiebig HH, Schuchardt C, Koch H, Strecker EP (1983) Mikroangiographische Untersuchungen verschiedener menschlicher Tumoren nach Transplantation auf thymusaplastischen Nacktmäuse. Res Exp Med (Berl) 182:63–70

    Google Scholar 

  • Mlynek ML, van Beuningen D, Leder LD, Streffer C (1985) Measurement of the grade of vascularisation in histological tumour tissue sections. Br J Cancer 52:945–948

    Google Scholar 

  • Müller O (1939) Die feinsten Blutgefäße des Menschen. Enke, Stuttgart

    Google Scholar 

  • Peterson HI (1979) Vascular and extravascular spaces in tumors: tumor vascular permeability. In: Peterson H-I (eds) Tumor blood circulation, CRC Press, Boca Raton, Florida, pp 77–86

    Google Scholar 

  • Peterson HI (1983) Innervation von Tumorblutgefäßen, Einfluß vasoaktiver Substanzen und Regulation der Tumordurchblutung. In: Meßmer K, Hammersen F (eds) Mikrozirkulation in Forschung und Klinik. (Structure and function of endothelial cells, vol 1). Karger, Basel, pp 69–77

    Google Scholar 

  • Revesz L, Siracka E (1984) Tumor vascularization, hypoxia, staging of tumors and radiocurability. Strahlenther Onkol 160:658–660

    Google Scholar 

  • Reynolds ES (1963) The use of lead citrate at high pH as an electron opaque stain in electron microscopy. J Cell Biol 17:208–212

    Google Scholar 

  • Richardson KC, Jarett L, Finke EH (1960) Embedding in epoxy resins for ultrathin sectioning in electron microscopy. Stain Technol 35:313–323

    Google Scholar 

  • Rubin H (1985) Cancer as a dynamic development disorder. Cancer Res 45:2935–2942

    Google Scholar 

  • Rubin R, Casarett G (1966a) Microcirculation of tumors. I. Anatomy, function, and necrosis. Clin Radiol 17:220–229

    Google Scholar 

  • Rubin R, Casarett G (1966b) Microcirculation of tumors. II. The supervascularized state in irradiated regressing tumors. Clin Radiol 17:346–355

    Google Scholar 

  • Sander A (1988) Vaskularisation und Proliferation in humanen Rektumkarzinomen. Dissertation, Universität Essen

  • Scherer E (1986) Warum Suche nach Individualisierung bei der radiologischen Tumortherapie? Strahlenther Onkol 162:621–623

    Google Scholar 

  • Schirrmacher V (1985) Cancer metastasis: experimental approaches, theoretical concepts and impacts for treatment strategies. Adv Cancer Res 43:1–73

    Google Scholar 

  • Schwarz G (1909) Über Desensibilisierung gegen Röntgen- und Radiumstrahlen. Münch Med Wochenschr 56:1217–1218

    Google Scholar 

  • Shubik P (1982) Vascularisation of tumours: a review. J Cancer Res Clin Oncol 103:211–226

    Google Scholar 

  • Siracka E, Siracka J, Pappova N, Revesz L (1982) Vascularisation and radiocurability in cancer of the uterine cervix. A retrospective study. Neoplasma 29:183–188

    Google Scholar 

  • Solesvik OV, Rofstad EK, Brustad T (1982) Vascular structure of five human malignant melanomas grown in athymic nude mice. Br J Cancer 46:557–567

    Google Scholar 

  • Song CW (1978) Effect of hyperthermia on vascular functions of normal tissues and experimental tumors. J Natl Cancer Inst 60:711–713

    Google Scholar 

  • Song CW, Rhee JG, Levitt SH (1980) Blood flow in normal tissues and experimental tumors. J Natl Cancer Inst 64:119–124

    Google Scholar 

  • Song CW, Lin JC, Chelstrom LM, Levitt BS, Levitt SH (1989) The kinetics of vascular thermotolerance in SCK tumors of A/J mice. Int J Radiat Oncol Biol Phys 17:799–802

    Google Scholar 

  • Steinberg F, Konerding MA, Donhuijsen K, Budach V, Streffer C (1989) Investigations on the individuality of tumours from 20 xenotransplanted sarcomas on nude mice. Strahlenther Onkol 165:504–505

    Google Scholar 

  • Streffer C (1987) Predictive assays of human tumour response. Introductory review. (Proc 8th ICRR) Radiol Res 2:825–830

    Google Scholar 

  • Sutherland RM (1988) Cell and environment interactions in tumor microregions: the multicell spheroid model. Science 240:177–184

    Google Scholar 

  • Takahashi M (1987) Farbatlas der onkologischen Zytologie. Perimed, Erlangen, S 62–65

    Google Scholar 

  • Tannock IF (1970) The relation between cell proliferation and the vascular system in a transplanted mouse mammary tumour. Br J Cancer 22:258–273

    Google Scholar 

  • Tannock IF, Steel GG (1969) Quantitative techniques for study of the anatomy and function of small blood vessels in tumors. J Nat Cancer Inst 42:771–782

    Google Scholar 

  • Vaupel P (1979) Oxygen supply to malignant tumors. In: Peterson HI (eds) Tumor blood circulation. CRC Press, Boca Raton, Florida, pp 143–168

    Google Scholar 

  • Vaupel P, Gabbert H (1986) Evidence for and against a tumor typespecific vascularity. Strahlenther Onkol 162:633–638

    Google Scholar 

  • Vaupel P, Frinak S, Bicher HI (1981) Heterogeneous oxygen partial pressure and pH distribution in C3H mouse mammary adenocarcinoma. Cancer Res 41:2008–2013

    Google Scholar 

  • Vaupel P, Fortmeyer HP, Runkel S (1987) Blood flow, oxygen consumption, and tissue oxygenation of human breast cancer xenografts in nude rats. Cancer Res 47:3496–3503

    Google Scholar 

  • Walmsley JG, Granter SR, Hacker MP, Moore AL, Ershler WB (1987) Tumor vasculature in young and old hosts: scanning electron microscopy of microcorrosion casts with microangiography, light microscopy and transmission electron microscopy. Scanning Microsc 1:823–830

    Google Scholar 

  • Warren BA (1979a) The vascular morphology of tumors. In: Petersen HI (eds) Tumor blood circulation: angiogenesis, vascular morphology and blood flow of experimental and human tumors. CRC Press, Boca Raton, Florida, pp 1–47

    Google Scholar 

  • Warren BA (1979b) Tumor angiogenesis. In: Peterson HI (eds) Tumor blood circulation: Angiogenesis, vascular morphology and blood flow of experimental and human tumors, CRC Press, Boca Raton, Florida, pp 49–75

    Google Scholar 

  • Yaes RJ (1989) Tumor heterogeneity, tumor size and radioresistance. Int J Radiat Oncol Biol Phys 17:993–1005

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Medical Radiation Biology, University of Essen, Federal Republic of Germany

    F. Steinberg & C. Streffer

  2. Institute of Anatomy, University of Essen, Federal Republic of Germany

    M. A. Konerding

Authors
  1. F. Steinberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. A. Konerding
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Streffer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Steinberg, F., Konerding, M.A. & Streffer, C. The vascular architecture of human xenotransplanted tumors: histological, morphometrical, and ultrastructural studies. J Cancer Res Clin Oncol 116, 517–524 (1990). https://doi.org/10.1007/BF01613005

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01613005

Key words

Search

Navigation