Alpha4 chain laminins are widely expressed in renal cell carcinomas and have a de-adhesive function.
Laminin (Lm) alpha4 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 alpha4 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 alpha4 chain was found in vasculature and stroma. Basement membranes were detected around tumor cell islets in 34/37 tumors. They showed immunoreactivity for Lm alpha4 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 alpha4 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 alpha4 chain Lms have a de-adhesive function and could thus play a role in detachment, migration and invasion of renal carcinoma cells in vivo.
Vainionpää
Noora
N
Institute of Biomedicine/Anatomy, University of Helsinki, Helsinki, Finland. noora.vainionpaa@helsinki.fi
Lehto
Veli-Pekka
VP
Tryggvason
Karl
K
Virtanen
Ismo
I
D014408:Biomarkers, Tumor / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000556:secondary; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D005353:Fibronectins / Q000502:physiology; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D007797:Laminin / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology
D014408:Biomarkers, Tumor; D005353:Fibronectins; C501369:LAMA4 protein, human; D007797:Laminin; D011994:Recombinant Proteins