1. ¹Division of Structural Cell Biology, Nara Institute of Science and Technology (NAIST), 8916-5 Takayama, Ikoma, Nara 630-0101, Japan
2. ²Department of Pathology, School of Allied Health Science, Faculty of Medicine, Osaka University, 1-7 Yamada-oka, Suita, Osaka 565-0817, Japan
3. ³Department of Vascular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA

Correspondence: Dr N Matsuura, E-mail: matsuura@sahs.med.osaka-u.ac.jp

Received 17 April 2002; Revised 10 October 2002; Accepted 18 October 2002.

Abstract

Tumour metastasis is known clinically to have organ specificity. We hypothesised that integrins might be involved in determining the organ specificity of tumour metastasis. Here, we report the results of spontaneous metastasis tested in nude mice that were inoculated with Chinese hamster ovary (CHO) cells expressing integrin 51 at various levels. The growth of the primary tumour inversely correlated with the 5 expression level on CHO cells, which is consistent with a previous report (Schreiner et al, 1991). The rates of pulmonary, lymph node, and adrenal metastases that developed in nude mice were not related to changes of the 5 expression level on CHO cells. Kidney metastasis developed in 40% of nude mice inoculated with 5B2 cells (CHO cells overexpressing 5) and in 20% of mice with CHO-K1 cells (CHO cells expressing native 5), whereas inoculation with CHO-B2 cells (5-defective mutants) and 5CHO cells with the highest expression of 5 did not lead to development of kidney metastasis. Furthermore, 5CHO, which shows the slowest growth of these cell types, did not lead to primary tumours in nude mice. These findings suggest that there is an appropriate level of 5 expression on tumour cells that leads to metastasis. Microscopic observations revealed that micrometastasis in the kidney was formed in glomeruli. An adhesion assay using frozen sections of the kidney demonstrated that 5B2 cells, but not CHO-B2 cells, effectively adhered to glomeruli. Kidney metastasis in vivo and the adhesion of 5B2 to glomeruli shown ex vivo were significantly suppressed by the administration of GRGDS peptide. Finally, we conclude that the interaction of 51 on tumour cells with fibronectin in kidney glomeruli is involved in kidney metastasis and that the tumour has appropriate levels of integrins crucial for metastasis.