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Factor from Rat Liver with Antiinvasive Potential on Rat Ascites Hepatoma Cells¹

Department of Tumor Biochemistry, Research Institute, The Center for Adult Diseases, Osaka, Osaka 537, Japan

An acid/ethanol extract of normal rat liver, both in vitro and in vivo, inhibited the invasion by a highly invasive subpopulation of rat ascites hepatoma cells, AH 130 (LC-AH cells). The addition of 10–80 µg/ml extract inhibited the formation of penetrated colonies of LC-AH cells underneath the cultured mesothelial cell (M-cell) monolayer. The tumor cells pretreated with the extract showed the diminished colony formation. Preincubation of the extract with plasma membranes prepared from LC-AH cells abolished the effect of the extract, suggesting a binding of the inhibitory entity [tentatively termed as "invasion-inhibiting factor" (IIF)] to the tumor cell surface. The extract did not inhibit the growth of LC-AH cells, but suppressed their directed migration underneath the M-cell monolayer. A concomitant i.p. injection of the extract with LC-AH cells into rats prevented the invasion by tumor cells of the peritoneum and formation of tumor nodules in the peritoneum and mediastinum, indicating that IIF inhibited the tumor cell invasion and metastasis in vivo, as well.

Upon ultrafiltration and gel fractionation, about 60% of IIF activity was recovered in the fraction corresponding to the molecular weight in the range of M_r 3000–4000. This activity was heat-stable at 100°C at neutral pH but labile at acidic pH and was inactivated by the treatment with pronase. The rest of the activity of IIF was found in the fraction of more than M_r 25,000.

¹ This work was supported in part by a Grant-in-Aid for Cancer Research (No. 60010009) from the Ministry of Education, Japan, a Grant-in-Aid from the Ministry of Health and Welfare for a Comprehensive 10-Year Strategy of Cancer Control, and a grant from Osaka Association for the Prevention of Adult Diseases.

² To whom requests for reprints should be addressed.

Received 11/ 3/87. Revised 3/14/88. Accepted 3/21/88.