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Functional characterization of the microcirculation in tumors

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Summary

This review describes some aspects of tumor vessels and the influence of vasoactive agents on tumor blood flow, particularly the characteristic microcirculation of tumors with regard to its selective increase in blood flow. Elevation of blood pressure by infusion of angiotensin II produced a severalfold increase in tumor blood flow. The increase was selective and specific to the tumor vessels as long as the mean arterial blood pressure was kept under 150 mm Hg. Pressure elevation by angiotensin II also selectively increased tumor oxygen tension and influx of lymph flow from the primary transplanted lesion to the lymph node metastatic lesion. Newly devised techniques for analyzing microhemodynamics of tumor vessels showed that the velocity of tumor blood flow, the vascular area in tumor tissue, and the hydrostatic pressure difference between the tumor vessel and extravascular tissue were markedly enhanced. Thus, the extravasation of material into tumor tissues can be increased by the enhancement of blood flow. This demonstration allowed the development of a new approach to cancer chemotherapy, in which the delivery to tumor tissue of systemically administered anticancer drugs can be selectively enhanced.

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References

  1. Greene HSN: Heterologous transplantation of mammalian tumors. I. The transfer of rabbit tumors to alien species. J Exp Med 73: 461–474, 1941.

    Google Scholar 

  2. Gimbrone MAJr, Leapman SB, Cotran RS, Folkman J: Tumor dormancy in vivo by prevention of neovascularization. J Exp Med 136: 261–276, 1972.

    Google Scholar 

  3. Folkman J: Tumor angiogenesis factor. Cancer Res 34: 2109–2113, 1974.

    Google Scholar 

  4. Suzuki M, Abe I, Hori K, Saito S, Sato H: Characteristic blood circulation in tumor tissue, with reference to local permeation of drug in cancer chemotherapy. In: Proceedings of the 36th annual meeting of the Japanese Cancer Association, Tokyo. Tokyo: Japanese Cancer Association, 1977, p 149.

    Google Scholar 

  5. Suzuki M, Hori K, Abe I, Saito H: Characteristics of microcirculation in tumor. Jpn J Cancer Chemother 6 (Suppl II): 287–291, 1979.

    Google Scholar 

  6. Suzuki M, Hori K, Abe I, Saito S, Sato H: Characteristic microcirculation of tumor. J Jap Coll Angiol 19: 233–236, 1979.

    Google Scholar 

  7. Suzuki M, Hori K, Abe I, Saito S, Sato H: Experimental study on characteristics of microcirculation in tumor tissue, with reference to cancer chemotherapy. In: Hellmann K, Hilgard P, Eccles S (eds) Metastasis: Clinical and Experimental Aspects. Martinus Nijhoff, The Hague, 1980, pp 356–360.

    Google Scholar 

  8. Suzuki M, Hori K, Abe I, Saito S, Sato H: A new approach to cancer chemotherapy: Selective enhancement of tumor blood flow with angiotensin II. J Natl Cancer Inst 67: 663–669, 1981.

    Google Scholar 

  9. Sato H, Suzuki M: Difference and agreement between the primary lesion and metastasis of cancer, with reference to the stroma of the tumor. Jpn J Clin Oncol 11 (Suppl): 159–166, 1981.

    Google Scholar 

  10. Suzuki M, Hori K, Abe I, Saito S, Sato S: Functional characteristic of tumor vessels, with reference to enhancement of the drug delivery. Jap J Cancer Clin 28: 592–598, 1982.

    Google Scholar 

  11. Suzuki M, Hori K, Abe I, Saito S, Sato H: Microcirculation of tumor concerning cancer chemotherapy. Tohoku Igaku Z 94: 44–46, 1981.

    Google Scholar 

  12. Hori K, Suzuki M, Abe I, Saito S, Sato H: New technique for measurement of microvascular pressure in normal and tumor vessels of rats. Invasion Metastasis 1: 248–260, 1981.

    Google Scholar 

  13. Hori K, Suzuki M, Abe I, Saito S, Sato H: Increase in tumor microvascular pressure by angiotensin-induced hypertension: Implication for pharmacokinetic analysis of drug delivery into tumor tissue. Jpn J Cancer Chemother 10: 953–960, 1983.

    Google Scholar 

  14. Sato H, Sato K, Sato Y, Mimata Y, Asamura M, Kanamaru R, Wakui A, Suzuki M, Sato H: Clinical study on selective enhancement of drug delivery by angiotensin II in cancer chemotherapy. In: Hellmann K, Hilgard P, Eccles S (eds) Metastasis: Clinical and Experimental Aspects. Martinus Nijhof, The Hague, 1980, pp 388–394.

    Google Scholar 

  15. Sato H, Sato K, Sato Y, Asamura M, Kanamaru R, Sugiyama Z, Kitahara T, Mimata Y, Wakui A, Suzuki M, Hori K, Abe I, Saito S, Sato H: Induced hypertension chemotherapy of cancer patients by selective enhancement of drug delivery to tumor tissue with angiotensin II. Sci Rep Res Inst Tohoku Univ-C 28: 32–44, 1981.

    Google Scholar 

  16. Wakui A, Suzuki M: Cancer chemotherapy in combination with angiotensin-induced hypertension. Jpn J Cancer Chemother 10: 1577–1583, 1983.

    Google Scholar 

  17. Ide AG, Baker NH, Warren SL: Vascularization of the Brown-Pearce rabbit epithelioma transplant as seen in the transparent ear chamber. Am J Roentgenol 42: 891–899, 1939.

    Google Scholar 

  18. Algire GH, Chalkely HW, Legallais FY, Park HD: Vascular reactions of normal and malignant tissues in vivo. 1. Vascular reactions of mice to wounds and to normal and neoplastic transplants. J Natl Cancer Inst 6: 73–85, 1945.

    Google Scholar 

  19. Greenblatt M, Shubik P: Tumor angiogenesis. Transfilter diffusion studies in the hamster by the transparent chamber technique. J Natl Cancer Inst 41: 111–124, 1968.

    Google Scholar 

  20. Cavallo T, Sade R, Folkman J, Cotran RS: Tumor angiogenesis. Rapid induction of endothelial mitoses demonstrated by autoradiography. J Cell Biol 54: 408–420, 1972.

    Google Scholar 

  21. Folkman J: tumor angiotenesis. Therapeutic implications. N Eng J Med 285: 1182–1186, 1971.

    Google Scholar 

  22. Folkman J, Merler E, Abernathy C, Williams G: Isolation of a tumor factor responsible for angiotenesis. J Exp Med 133: 275–288, 1971.

    Google Scholar 

  23. Ziche M, Jones J, Gullino PM: Role of prostaglandin E1 and copper in angiogenesis. J Natl Cancer Inst 69: 475–482, 1982.

    Google Scholar 

  24. Yamaura H, Sato H: Quantitative studies on the developing vascular system of the hepatoma. J Natl Cancer Inst 53: 1229–1240, 1974.

    Google Scholar 

  25. Warren BA, Shubik P: The growth of the blood supply to melanoma transplants in the hamster cheek pouch. Lab Invest 15: 464–478, 1966.

    Google Scholar 

  26. Muthukkarppan VR, Kubai L, Auerback R: Tumor-induced neovascularization in the mouse eye. J Natl Cancer Inst 69: 699–708, 1982.

    Google Scholar 

  27. Gimbrone MA, Cotran RS, Leapman SB, Folkman J: Tumor growth and neovascularization. An experimental model using the rabbit cornea. J Natl Cancer Inst 52: 413–427, 1974.

    Google Scholar 

  28. Warren BA: The ultrastructure of the microcirculation at the advancing edge of Walker 256 carcinoma. Microvasc Res 2: 443–453, 1970.

    Google Scholar 

  29. Eddy HA, Casarett W: Development of vascular system in the hamster malignant neurilemmoma. Microvasc Res 6: 63–82, 1973.

    Google Scholar 

  30. Reinhold HS: Improved microcirculation in irradiated tumors. Eur J Cancer 7: 273–280, 1971.

    Google Scholar 

  31. Kjartansson I: Tumour circulation. An experimental study in the rat with a comparison of different methods for estimation of tumour blood flow. Acta Chir Scand Suppl 471: 1–74, 1976.

    Google Scholar 

  32. Endrich B, Reinhold HS, Gross JF, Intaglietta M: Tissue perfusion inhomogeneity during early tumor growth in rats. J Natl Cancer Inst 62: 387–395, 1979.

    Google Scholar 

  33. Peterson H-I: Tumor blood flow compared with normal tissue blood flow. In: Peterson H-I (ed) Tumor blood flow. CRC Press. Florida, 1979, pp 103–114.

    Google Scholar 

  34. Thomlinson RH, Gray LH: The histological structure of some human lung cancers and the possible implications for radiotherapy. Brit J Cancer 9: 539–549, 1955.

    Google Scholar 

  35. Warren BA: The vascular morphology of tumors. In: Peterson H-I (ed) Tumor blood flow. CRC Press, Florida, 1979, pp 1–47.

    Google Scholar 

  36. Krylova NV: Characteristics of microcirculation in experimental tumors. Bibl Anat 10: 301–303, 1969.

    Google Scholar 

  37. Kligerman MM, Henel DK: Some aspects of the microcirculation of a transplantable experimental tumor. Radiology 76: 810–817, 1961.

    Google Scholar 

  38. Gullino PM, Grantham FH: Studies on the exchange of fluids between host and tumor. III. Regulation of blood flow in hepatomas and other rat tumors. J Natl Cancer Inst 28: 211–229, 1962.

    Google Scholar 

  39. Cater DB, Adair HM, Grove CA: Effects of vasomotor drugs and ‘mediators’ of the inflammatory reaction upon the oxygen tension of tumours and tumour blood-flow. Br J Cancer 20: 504–516, 1966.

    Google Scholar 

  40. Edlich RF, Rogers W, DeShazo CVJr, Aust JB: Effect of vasoactive drugs on tissue blood flow in the hamster melanoma. Cancer Res 26: 1420–1424, 1966.

    Google Scholar 

  41. Rankin JH, Jirtle R, Phernetton TM: Anomalous responses of tumor vasculature to norepinephrine and prostaglandin E2 in the rabbit. Circ Res 41: 496–502, 1977.

    Google Scholar 

  42. Kruuv JA, Inch WR, McCredie JA: Blood flow and oxygenation of tumors in mice. II. Effects of vasodilator drugs. Cancer 20: 60–65, 1967.

    Google Scholar 

  43. Wickersham JK, Barrett WP, Furukawa SB, Puffer HW, Warner NE: An evaluation of the response of the microvasculature in tumors in C3H mice to vasoactive drugs. Bibl Anat 15: 291–293, 1977.

    Google Scholar 

  44. Ackerman NB, Hechmer PA: Effects of phamacological agents on the microcirculation of tumors implanted in the liver. Bibl Anat 15: 301–303, 1977.

    Google Scholar 

  45. Mattson J, Appelgren L, Karlsson L, Peterson HI: Influence of vasoactive drugs and ischaemia on intra-tumour blood flow distribution. Eur J Cancer 14: 761–764, 1978.

    Google Scholar 

  46. Jirtle R, Clifton KH, Rankin JHG: Effects of several vasoactive drugs on the vascular resistance of MT-W9B tumors in W/Fu rats. Cancer Res 38: 2385–2390, 1978.

    Google Scholar 

  47. Young SW, Hollenberg NK, Kazam E, Berkowitz DM, Hainen R, Sandor T, Abrams HL: Resting host and tumor perfusion as determinants of tumor vascular responses to norepinephrine. Cancer Res 39: 1898–1903, 1979.

    Google Scholar 

  48. Takács L, Debreczeni LA, Farsang Cs: Regional vascular reactivity in rats with Guerin carcinoma (GC). Experientia 35: 1238–1240, 1979.

    Google Scholar 

  49. Hafström L, Nobin A, Persson B, Sundqvist K: Effects of catecholamines on cardiovascular response and blood flow distribution to normal tissue and liver tumors in rats. Cancer Res 40: 481–485, 1980.

    Google Scholar 

  50. Kaelin WGJr, Shrivasta S, Shand DG, Jirtle RL: Effect of verapamil on malignant tissue blood flow in SMT-2A tumor-bearing rats. Cancer Res 42: 3944–3949, 1982.

    Google Scholar 

  51. Mattson J, Peterson H-I: Influence of vasoactive drugs on tumour blood flow (Review). Anticancer Res 1: 59–61. 1981.

    Google Scholar 

  52. Young SW, Muller HH, Marincek B: Response of neoplastic and normal vasculature to acetylcholine. Eur J Cancer Clin Oncol 9: 383–387, 1983.

    Google Scholar 

  53. Häggendal E, Johansson B: On the pathophysiology of the increased cerebrovascular permeability in acute arterial hypertension in cats. Acta Neurol Scand 48: 265–270, 1972.

    Google Scholar 

  54. Suzuki T, Tominaga S, Strandgaard S, Nakamura T: Fluorescein cineangiography of the pial microcirculation in the rat in acute angiotensin-induced hypertension. In: Harper M, Jennett B, Miller D, Rowan J (eds) Blood flow and metabolism in the brain. Churchill-Livingstone, Edinburgh, 1975, pp 5.8–5.9.

    Google Scholar 

  55. MacKenzie ET, Strandgaard S, Graham DI, Jones JV, Harper AM, Farrar JK: Effects of acutely induced hypertension in cats on pial arteriolar caliber, local cerebral blood flow, and the blood-brain barrier. Circ Res 39: 33–41, 1976.

    Google Scholar 

  56. Suzuki M, Abe I, Sato H: Changes in drug delivery (by blood-brain barrier dysfunction) on arachnoid leukemia: implication for CNS leukemic dissemination. Clin Expl Metastasis 1: 163–171, 1983.

    Google Scholar 

  57. Semple SJG, de Wardener HE: Effect of increased renal venous pressure on circulatory ‘autoregulation’ of isolated dog kidneys. Circ Res 7: 643–648, 1959.

    Google Scholar 

  58. Algire GH, Legallais FY, Anderson BF: Vascular reaction of normal and malignant tissues in vivo. VI. The role of hypotension in the action of components of podophyllin on transplanted sarcomas. J Natl Cancer Inst 14: 879–893, 1954.

    Google Scholar 

  59. Gullino PM, Grantham PH: Studies on the exchange of fluides between host and tumor. II. The blood flow of hepatomas and other tumors in rats and mice. J Natl Cancer Inst 27: 1465–1491, 1961.

    Google Scholar 

  60. Rogers W, Edlich RF, Lewis DV, Aust JB: Tumor blood flow. I. Blood flow in transplantable tumors during growth. Surg Clin N America 47: 1473–1482, 1967.

    Google Scholar 

  61. Cataland S, Cohen C, Sapirstein LA: Relationship between size and perfusion rate of transplanted tumors. J Natl Cancer Inst 29: 389–394, 1962.

    Google Scholar 

  62. Vaupel P: Interrelationship between mean arterial blood pressure, blood flow, and vascular resistance in solid tumor tissue of DS-Carcinosarcoma. Experienta 31: 587–589, 1975.

    Google Scholar 

  63. Edlich RF, Borner J, Buchin RJ: Microcirculation of tumor Influence of implantation site on tumor blood flow. Arch Surg 98: 233–234, 1969.

    Google Scholar 

  64. Young SW, Hollenberg NK, Abrams HL: The influence of implantation site on tumor growth and blood flow. Eur J Cancer 15: 771–777, 1979.

    Google Scholar 

  65. Endrich B, Intaglietta M, Reinhold HS, Gross JF: Hemodynamic characteristics in microcirculatory blood channels during early tumor growth. Cancer Res 39: 17–23, 1979.

    Google Scholar 

  66. Hori K, Suzuki M, Abe I, Saito S, Sato H: A micro-occlusion technique for measurement of the microvascular pressure in tumor and subcutis. Gann 74: 122–127, 1983.

    Google Scholar 

  67. Peters W, Teixeira M, Intaglietta M, Gross JF: Microcirculatory studies in rat mammary carcinoma. I. Transparent chamber method, development of microvasculature, and pressures in tumor vessels. J Natl Cancer Inst 65: 631–642, 1980.

    Google Scholar 

  68. Butler TP, Grantham FH, Gullino PM: Bulk transfer of fluid in the interstitial component of mammay tumors. Cancer Res 35: 3084–3088, 1975.

    Google Scholar 

  69. Hori K, Suzuki M, Abe I, Saito S, Sato H: Change in pressure difference between intra- and extravascular space in tumor tissue by angiotensin-induced hypertension. In: Proceedings of the 41st annual meeting of the Japanese Cancer Association, Osaka. Japanese Cancer Association, Tokyo, 1982, p 234.

    Google Scholar 

  70. Suzuki M, Hori K, Abe I, Saito S, Sato H: Characteristics of microcirculation in methylcholanthrene-induced primary tumors and in lymphnode metastasis. In: Proceedings of the 38th annual meeting of the Japanese Cancer Association, Tokyo, Japenese Cancer Association, Tokyo, 1979, p 298.

    Google Scholar 

  71. Gray LH, Conger AD, Ebert M, Hornsey S, Scott OCA: The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol 26: 638–648, 1953.

    Google Scholar 

  72. Vaupel P: Hypoxia in neoplastic tissue. Microvasc Res 13: 399–408, 1977.

    Google Scholar 

  73. Suzuki M, Hori K, Abe I, Saito S, Sato H: Selective increase in tumor oxygen tension with angiotensin II. Invasion Metastasis 2: 33–39, 1982.

    Google Scholar 

  74. Ichimura H: Experimental studies on a screening system of anticancer drugs employing the rat ascites hepatoma spectrum. Jpn J Cancer Chemother 2: 605–610, 1975.

    Google Scholar 

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Authors and Affiliations

  1. Department of Oncology, The Research Institute for Tuberculosis and Cancer, Tohoku University, 4-1 Seiryomachi, 980, Sendai, Japan

    Maroh Suzuki, Katsuyoshi Hori, Ikuo Abe, Sachiko Saito & Haruo Sato

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  1. Maroh Suzuki
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  2. Katsuyoshi Hori
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  4. Sachiko Saito
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  5. Haruo Sato
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Suzuki, M., Hori, K., Abe, I. et al. Functional characterization of the microcirculation in tumors. Cancer Metast Rev 3, 115–126 (1984). https://doi.org/10.1007/BF00047659

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