Skip to main content
PMC home page
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1991 Jan;82(1):109–117. doi: 10.1111/j.1349-7006.1991.tb01753.x

Characterization of Heterogeneous Distribution of Tumor Blood Flow in the Rat

Katsuyoshi Hori 1, March Suzuki 1, Shigeru Tanda 1, Sachiko Saito 1
PMCID: PMC5918220  PMID: 1705537

Abstract

Angioarchitectures of ascites hepatoma AH109A and Sato lung carcinoma (SLC) were quantitatively compared by measuring the following morphometric parameters: vascular density, vascular length, distance hetween tissues and their nearest blood vessel, and total length of microvascular network per unit area. When the vascular networks in these two types of tumors were compared in the initial stage, the morphological parameters were almost identical. Correlations between tumor size and the number of starting vessels and between enlargement of the tumor and the ensuing increase in pressure of the starting vessel were also evaluated with a microcomputer and an apparatus for measuring micro–vascular pressure. The total length of tumor vascular network to which one starting vessel supplied blood increased exponentially as the tumor increased in size exponentially. There was a positive correlation between tumor size and the number of starting vessels. The range of the blood supply from one starting vessel was evidently limited. The pressure of the starting vessel increased with enlargement of the tumor size. As soon as the pressure of the starting vessel reached a plateau, however, there was a rapid increase in low–flow or no–flow areas in regions within the tumor. From the results obtained, we consider that low–flow or no–flow areas, resistant to delivery of anticancer drugs, inevitably appear with the progression of tumor growth.

Keywords: In vivo analysis, Tumor blood flow, Vascular structure, Starting vessel, No, flow area

Full Text

The Full Text of this article is available as a PDF (811.0 KB).

REFERENCES

  • 1. ) Suzuki , M , Hori , K. , Abe , I. , Saito , S. and Sato , H.Functionalcharacterizationof the microcirculationin tumors . Cancer Metastasis Rev. , 3 , 115 – 126 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Jain , R. K.Determinants of tumor blood flow: a review . Cancer Res. , 48 , 2641 – 2658 ( 1988. ). [PubMed] [Google Scholar]
  • 3. ) Brown , J. M.Evidence for acutely hypoxic cells in mouse tumours, and a possible mechanism of reoxygenation . Br. J. Radiol. , 52 , 650 – 656 ( 1979. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Hori , K. , Suzuki , M. , Abe , I. , Saito , S. and Sato , H.Increase in tumor microvascular pressure by angiotensininduced hypertension: implication for pharmacokinetic analysis of drug delivery into tumor tissue . Jpn. J. Cancer Chemother. , 10 , 953 – 960 ( 1983. ) ( in Japanese ). [PubMed] [Google Scholar]
  • 5. ) Ackerman , N. B. and Makohon , S.The blood supply of experimental liver metastasis. VII. Further studies on increased tumor vascularity caused by epinephrine . Microcirc. Endothelium Lymphatics , 1 , 547 – 568 ( 1984. ). [PubMed] [Google Scholar]
  • 6. ) Chaplin , D. J. , Durand , R. E. and Olive , P. L.Acute hypoxia in tumors: implications for modifiers of radiation effects . Int. J. Radiat. Oncol. Biol Phys. , 12 , 1279 – 1282 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Hori , K. , Suzuki , M. , Tanda , S. and Saito , S.In vivo analysis of tumor vascularization in the rat . Jpn. J. Cancer Res. , 81 , 279 – 288 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. ) Hori , K. , Suzuki , M. , Abe , I and Saito , S.Rat transparent chamber techniquesfor morphologicalandfunctional analysis in microcirculation . Kokenshi , 37 , 269 – 278 ( 1985. ) ( in Japanese ). [Google Scholar]
  • 9. ) Hori , K. , Suzuki , M. , Saito , S. , Tanda , S. , Li , Y. and Zhang , Q. H.A new anesthetic machine for small laboratory animals . Kokenshi , 40 , 305 – 310 ( 1988. ) ( in Japanese ). [Google Scholar]
  • 10. ) Engelson , E. T. , Schmid‐Schönbein , G. W. and Zweifach , B. W.The microvasculature in skeletal muscle II. Arteriolar network anatomy in normotensive and spontaneously hypertensive rats . Micmvasc. Res. , 31 , 356 – 374 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Yamaura , H. and Sato , H.Quantitative studies on the developing vascular system of rat hepatoma . J. Natl. Cancer Inst , 53 , 1229 – 1240 ( 1974. ). [DOI] [PubMed] [Google Scholar]
  • 12. ) Chalkley , H. W.Method for quantitative morphologic analysis of tissue . J. Natl. Cancer Inst. , 4 , 47 – 53 ( 1943. ). [Google Scholar]
  • 13. ) Skalak , T. C. and Schmid‐Schonbein , G. W.The microvasculature in skeletal muscle IV. A model of the capillary network . Microvase. Res. , 32 , 333 – 347 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Hori , K. , Suzuki , M. , Abe , L , Saito , S. and Sato , H.A micro–occlusion technique for measurement of the microvascular pressure in tumor and subcutis . Gann , 74 , 122 – 127 ( 1983. ). [PubMed] [Google Scholar]
  • 15. ) Wiedeman , M. P.Architecture . Handb. Physiol. Sect. 2: Cardiovasc. Syst. , 4 , 11 – 40 ( 1984. ). [Google Scholar]
  • 16. ) Lewis , W. H.The vascular pattern of tumors . Bull Johns Hopkins Hosp. , 41 , 156 – 162 ( 1927. ). [Google Scholar]
  • 17. ) Goodall , C. M. , Sanders , A. G. and Shubik , P.Studies of vascular patterns in living tumors with a transparent chamber inserted in hamster cheek pouch . J. Natl. Cancer Inst , 35 , 497 – 521 ( 1965. ). [DOI] [PubMed] [Google Scholar]
  • 18. ) Rubin , P. and Casarett , G.Microcirculation of tumors. Part I: Anatomy, function, and necrosis . Clin. Radiol , 17 , 220 – 229 ( 1966. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Falk , P.Patterns of vasculature in two pairs of related fibrosarcomas in the rat and their relation to tumour responses to single large doses of radiation . Eur. J. Cancer , 14 , 237 – 250 ( 1978. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Egawa , J. , Ishioka , K. and Ogata , T.Vascular structure of experimental tumours . Acta Radial. Oncol. , 18 , 367 – 375 ( 1979. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Gabbert , H. , Wagner , R. and Hohn , P.The relation between tumor cell proliferation and vascularization in differentiated and undifferentiated colon carcinomas in the rat . Virchows Arch. (Cell. Pathol.) , 41 , 119 – 131 ( 1982. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Solesvik , O. V. , Rofstad , E. K. and Brustad , T.Vascular structure of five human malignant melanomas grown in athymic nude mice . Br. J. Cancer , 46 , 557 – 567 ( 1982. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. ) Algire , G. H , and Chalkley , H. W.Vascular reactions of normal and malignant tissues in vivo. I. Vascular reactions of mice to wounds and to normal and neoplastic transplants . J. Natl. Cancer Inst. , 6 , 73 – 85 ( 1945. ). [Google Scholar]
  • 24. ) Suzuki , M. , Takahashi , T. and Sato , T.The medial regression in tumor–bearing host arteries and its functional significance: a morphometric study of hepatic arteries in human livers with hepatocellular carcinomas . Cancer , 59 , 444 – 450 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 25. ) Yaegashi , H. and Takahashi , T.Encasement and other deformations of tumor–embedded host arteries due to loss of medial smooth muscle. Morphometric and three–dimensional reconstruction studies on some human carcinomas . Cancer , 65 , 1097 – 1103 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 26. ) Nugent , L. J. and Jain , R. K.Extravascular diffusion in normal and neoplastic tissues . Cancer Res. , 44 , 238 – 244 ( 1984. ). [PubMed] [Google Scholar]
  • 27. ) Heuser , L. S. and Miller , F. N.Differential macromolecular leakage from the vasculature of tumors . Cancer , 57 , 461 – 464 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 28. ) Hori , K. , Suzuki , M. , Abe , S. and Saito , S.Changes in tumor transvascular pressure difference associated with tumor growth: implications for angiotensin–induced hypertension chemotherapy . Jpn. J. Cancer Chemother. , 12 , 1630 – 1637 ( 1985. ) ( in Japanese ). [PubMed] [Google Scholar]
  • 29. ) Hori , K. , Suzuki , M. , Saito , S. , Tanda , S. and Zhang , Q. H.Fluctuation of tumor blood flow under normotension; implication for induced hypertension chemotherapy . Proc. Jpn. Cancer Assoc., 47th Annu. Meet. , 550 ( 1988. )( in Japanese ). [Google Scholar]
  • 30. ) Hori , K. , Suzuki , M. , Saito , S. and Tanda , S.Development of the angioarchitecture and microcirculatory characteristics in rat tumor . Jpn. J. Cancer Chemother. , 17 , 554 – 563 ( 1990. ) ( in Japanese ). [PubMed] [Google Scholar]
  • 31. ) Suzuki , M. , Hori , K. , Abe , L , Saito , S. and Sato , H.Characteristicblood circulationintumortissue, with reference to cancer chemotherapy . Jpn. J. Cancer Chemother. , 5 , 77 – 80 ( 1978. ) ( in Japanese ). [Google Scholar]
  • 32. ) Suzuki , M. , Hori , K. , Abe , I. , Saito , S. and Sato , H.A new approach to cancer chemotherapy. Selective enhancement of tumor blood flow with angiotensinll . J. Natl. Cancer Inst , 67 , 663 – 669 ( 1981. ). [PubMed] [Google Scholar]
  • 33. ) Hori , K. , Suzuki , M. , Abe , L , Saito , S. and Sato , H.Increase in tumor vascular area due to increased blood flow by angiotensin II in rats . J. Natl. Cancer Inst. , 74 , 453 – 459 ( 1985. ). [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES