1. ¹Institute of Biomedicine/Anatomy, University of Helsinki, Helsinki, Finland
2. ²Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland
3. ³Department of Medical Biochemistry and Biophysics, Division of Matrix Biology, Karolinska Institutet, Stockholm, Sweden

Correspondence: Dr N Vainionpää, MD, Institute of Biomedicine/Anatomy, University of Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014 Helsinki, Finland. E-mail: noora.vainionpaa@helsinki.fi

Received 20 March 2007; Revised 23 April 2007; Accepted 30 April 2007; Published online 4 June 2007.

Abstract

Laminin (Lm) 4 chain, a constituent of Lm-411 and Lm-421, is mainly localized to mesenchyme-derived tissues, and is suggested to have a role in formation and function of endothelium, transmigration of inflammatory cells through endothelium, and invasion of certain tumors. In this study, we evaluated the distribution of 4 chain Lms in 33 conventional (clear cell) renal cell carcinomas (RCCs) (31 primary tumors, two metastases), two papillary RCCs, and two oncocytomas by immunohistochemistry. In all tumors, immunoreactivity for Lm 4 chain was found in vasculature and stroma. Basement membranes were detected around tumor cell islets in 34/37 tumors. They showed immunoreactivity for Lm 4 chain in 28/34 cases. Northern blotting, inhibition of protein secretion with monensin, and immunoprecipitation combined with Western blotting showed that Caki-2, ACHN, and Caki-1 renal carcinoma cell lines produce 4 chain Lms. In cell adhesion assay, recombinant human Lm-411 did not promote adhesion of renal carcinoma cells but inhibited adhesion to fibronectin (Fn). In cell migration assay, the cells migrated more on Lm-411 than on Fn. The results suggest that 4 chain Lms have a de-adhesive function and could thus play a role in detachment, migration and invasion of renal carcinoma cells in vivo.