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Published online before print March 13, 2007, 10.1148/radiol.2432060341
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(Radiology 2007;243:386-395.)
© RSNA, 2007

Experimental Studies

Changes of Intratumoral Microvessels and Blood Perfusion during Establishment of Hepatic Metastases in Mice1

Yi Liu, MD2 and Osamu Matsui, MD

1 From the Department of Radiology, Kanazawa University, Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8641, Japan. Received February 22, 2006; revision requested April 25; revision received May 25; accepted June 20; final version accepted August 14. Supported in part by the Ministry of Education, Science, Sports and Culture, Grant-in-Aid for Scientific Research (C), 16591192, 2004, and by a Grant-in-Aid for Cancer Research (15) from the Ministry of Health, Labour and Welfare. Address correspondence to O.M. (e-mail: matsuio{at}med.kanazawa-u.ac.jp).

Purpose: To prospectively evaluate the stepwise changes that occur in intratumoral microvessels and microcirculation during the establishment of murine colonic hepatic metastases by using in vivo fluorescent microscopy and to compare the changes with tumor angiogenesis evaluated with an immunohistochemical study.

Materials and Methods: This study was approved by the institutional animal care and use committee. Twenty-five mice with hepatic metastases created with injection of murine colonic adenocarcinoma (colon 26) tumor cells into the spleen were examined with in vivo microscopy and immunohistochemical study for CD34, intracellular adhesion molecule (ICAM-1), and alpha smooth muscle actin ({alpha}-SMA). The tumor size, microcirculation in tumors, intratumoral microvessel density (MVD), afferent MVD, and CD34-positive MVD were evaluated. The data among the tumors that showed different hemodynamic or immunohistochemical patterns were compared with the Kruskal-Wallis test and the Student t test.

Results: Four stepwise patterns were observed according to the changes in morphology, hemodynamics, and immunohistochemical characteristics of intratumoral microvessels during the establishment of hepatic metastases, as follows: metastases without definite intratumoral blood perfusion or any intratumoral microvessels (mean diameter, approximately 180 µm), metastases with portal perfusion and intratumoral ICAM-1–positive residual hepatic sinusoids (mean diameter, approximately 290 µm), metastases with mixed portal and arterial perfusion and increased CD34-positive microvessels and {alpha}-SMA–positive arterioles (mean diameter, approximately 520 µm), and metastases with exclusively arterial perfusion and increased CD34-positive microvessels and {alpha}-SMA–positive arterioles (mean diameter, >2000 µm). The differences among the mean sizes of the tumors that showed these four patterns were statistically significant (P < .01).

Conclusion: Stepwise changes of intratumoral microcirculation were revealed from direct diffusion, to portal perfusion, to mixed portal and arterial perfusion, and finally to arterial perfusion in accordance with stepwise tumor neovascularization during the growth of murine colonic hepatic metastases.

© RSNA, 2007




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