Regular Article

British Journal of Cancer (2001) 85, 431–438. doi:10.1054/bjoc.2001.1911 www.bjcancer.com
Published online 31 July 2001

In vivo evaluation of the early events associated with liver metastasis of circulating cancer cells

L Ding1, M Sunamura1, T Kodama1, J Yamauchi1, D G Duda1, H Shimamura1, K Shibuya1, K Takeda1 and S Matsuno1

1First Department of Surgery, Tohoku University School of Medicine, Seiryo-cho 1-1, Aoba-ku, Sendai, 980-8574, Japan

Received 20 March 2000; Revised 5 March 2001; Accepted 7 March 2001.

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Abstract

The mechanism of metastasis formation remains still largely unknown. Many studies underline the importance and complexity of the initial arrest of the circulating tumour cells in the target organ, a key stage in metastasis occurrence. In our study, we evaluated by visual means the metastasis formation using an in vivo microscopy system in a murine model. Moreover, we investigated the involvement of P-selectin in these processes using immunohistochemistry and P-selectin knockout mice. The present study offers direct evidence of distinct pathways for tumour metastasis formation by a lymphoma cell – EL-4 and a solid tumour cell – C26. Off-line analysis of the images and histological data confirmed that mechanical entrapment of the solid tumour cell, which had a bigger diameter than that of the liver sinusoids, promoted metastasis without any detectable involvement of adhesion molecules. On the other hand, we observed that lymphoma cells, in spite of their smaller diameter as compared to the sinusoids, promoted liver metastasis as well, but with the essential participation in their arrest of P-selectin, indicating an adhesion molecule-mediated pathway. © 2001 Cancer Research Campaign

Keywords:

circulating tumour cells, liver microcirculation, P-selectin, knockout mouse, intravital microscopy

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