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M_r 92,000 Gelatinase Release Correlates with the Metastatic Phenotype in Transformed Rat Embryo Cells¹

Department of Pathology and Laboratory Medicine [E. J. B., R. J. M.] and Department of Radiation Oncology [E. N. H.], University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

In a previous study we described a correlation between the metastatic potential of transformed rat embryo cells (REC) and their release of type IV collagenolytic activity (S. Garbisa et al., Cancer Res., 47: 1523–1528, 1987). In the present study, we have identified a M_r 92,000 gelatinase released exclusively by metastatic cell lines in vitro; seven of eight highly metastic REC lines transformed by H-ras or H-ras plus v-myc released this enzyme. In contrast, the M_r 92,000 gelatinase was not detected in two separate nontumorigenic REC lines immortalized with H-ras or c-myc or in four independent tumorigenic REC lines (transformed by H-ras plus adenovirus E1A) with markedly reduced metastatic potential. Study of the M_r 92,000 gelatinase in tumor explants showed that its expression may be modulated in vivo. Not only was M_r 92,000 release enhanced in tumor explants from cell lines which released it in vitro, but its expression was evident in three primary tumors and six metastatic tumors from the one metastatic cell line that failed to release it in vitro. Explants from the nonmetastatic cell lines grown as tumors showed no M_r 92,000 gelatinase release. The heterogeneous expression of a number of other gelatinases with molecular weights of 52,000, 56,000 62,000, 68,000, 80,000, and 240,000 was observed, but no correlation with metastatic potential was apparent. The M_r 92,000 gelatinase had the characteristics of a secreted neutral metalloproteinase. It may be responsible for the type IV collagenolytic activity reported previously in conditioned medium from metastatic transformed REC and could in part be responsible for the differences in metastatic potential in these cell lines.

¹ This work has been supported by Grant CA 46830 from the NIH to R. J. M. E. B. has been supported by T32CA09140; R. J. M. is the recipient of a Junior Faculty Research Award and E. N. H., a Clinical Oncology Career Development Award from the American Cancer Society.

² To whom requests for reprints should be addressed, at Department of Radiation Oncology, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, PA 19104-4283.

Received 12/14/89. Revised 2/28/90.

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