Carbonyl reductase: A novel metastasis-modulating function

To explore reasons for differences in the malignancy of tumors, we have com pared two cell lines derived from a mouse lung adenocarcinoma cell line tha t differ ill-fold in their capacity to form lung metastases from s.c. prima ry tumors or after i.v. injection. One mRNA encoding carbonyl reductase was identified at a relatively high abundance in the subline with low metastat ic capacity but was not detectable in the highly metastatic subline. Transf ection of the former subline with a plasmid construct expressing antisense carbonyl reductase rendered the cells highly metastatic. Conversely, the ca pacity of the highly metastatic cells to metastasize was markedly reduced a fter transfection with a construct expressing carbonyl reductase, We also f ound that human prostate cancers show loss of carbonyl reductase expression compared with normal prostate epithelia, These data suggest that carbonyl reductase has an important function in modifying the metastatic behavior of malignant tumors.