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Elevation of Lysosomal Enzymes in Primary Lewis Lung Tumor Correlated with the Initiation of Metastasis¹

Department of Experimental Therapeutics, Grace Cancer Drug Center, New York State Department of Health, Roswell Park Memorial Institute, Buffalo, New York 14263

Lysosomal enzymes were elevated about two-fold in primary s.c. Lewis lung carcinoma as compared with metastatic nodules in the lung. In a time course experiment, a general two-fold elevation of acid phosphatase and several glycosidases was observed in the primary tumor between the 14th and 17th postimplant day following s.c. inoculation of Lewis lung carcinoma. This increase in hydrolytic enzyme activity was not due to necrosis in the primary tumor since a comparison of enzyme activities in the nonnecrotic and necrotic areas demonstrated much higher activities in the nonnecrotic areas. No increases in lysosomal enzyme activity were observed with time in Sarcoma 180, a tumor which does not metastasize. There was no change with time in primary Lewis lung tumor lactate dehydrogenase activity while a 7-fold increase in serum lactate dehydrogenase activity was observed in tumor-bearing mice. Mitochondrial succinate-2-(p-iodophenyl)-3-(p-nitrophenyl)-5-phenyltetrazolium reductase levels fell in the primary Lewis lung tumor as the tumor size increased. A positive correlation was observed between the time of the elevations of tumor lysosomal enzymes in Lewis lung carcinoma and the appearance of micro- and macrometastatic lesions in the lungs. The mechanisms accounting for the increased intratumoral lysosomal enzymes are unknown, but they may be related to macrophage infiltration or other tumor-host interactions which may facilitate the dissemination of tumor cells.

¹ The work reported in this paper was supported by Program Grant CA 13038 from the National Cancer Institute, Department of Health, Education and Welfare.

² Recipient of an American Cancer Society Eleanor Roosevelt International Fellowship awarded by the International Union Against Cancer.

³ Recipient of Grants CA 15757 and CA 19814. To whom requests for reprints should be addressed.

Received 11/ 1/79. Accepted 6/11/80.

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