Alterations in the distribution and activity of transglutaminase during tumour growth and metastasis

Abstract

Transglutaminase activity and subcellular distribution have been examined in both normal and tumour tissue. Subcellular fractionation of rat liver demonstrated a bimodial distribution for transglutaminase between the particulate (∼40%) and cytosol (∼60%) fractions. Isolation of enriched plasma membrane fractions indicated the presence of membrane associated transglutaminase activity which co-distributed with that of 5'-nucleotidase and Na ⁺ /K ⁺ -ATPase. Induction of hepatocellular carcinomas in rats by treatment with either diethylnitrosamine or 6-p-dimethylaminophenylazobenzothiazole resulted in a reduction in transglutaminase activity which was accompanied by redistribution of the enzyme to the particulate fraction of the cell. The tumour bearing liver appeared to represent an intermediate stage between the hepatocellular carcinoma and control liver when assayed for content and distribution of transglutaminase activity. The transglutaminase activity of four transplantable rat sarcomas (P ₇ , P ₈ , MC ₃ and CC ₅ ) was found to be greatly reduced when compared with the normal tissues of rat liver, lung and spleen. A further reduction in this activity occurred in the primary growths of the sarcomas P ₇ and P ₈ following detection of metastases. Our data suggest that such changes in the distribution and content of transglutaminase may be a feature of tumour tissue and may be of value in both monitoring and investigating the carcinogenic process.