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Destruction of Extracellular Matrices Containing Glycoproteins, Elastin, and Collagen by Metastatic Human Tumor Cells¹

Departments of Pediatrics [P. A. J., Y. A. D.] and Biochemistry [P. A. J.], University of Southern California School of Medicine, and Department of Pediatrics, Division of Hematology-Oncology, Childrens Hospital of Los Angeles, Los Angeles, California 90027

Four human tumor cell lines were grown in direct contact with the extracellular matrix proteins which had previously been produced by cultured rat smooth muscle cells. The extracellular matrix contained glycoproteins, elastin, and collagen, and its digestion by the tumor cells was followed by the appearance of radioactive breakdown products in the supernatant medium. All four tumor lines tested digested glycoproteins present in the matrix, whereas human fibroblasts were inactive in glycoprotein digestion. The human fibrosarcoma cell line (HT1080) demonstrated elastolytic and collagenolytic activity in addition to a plasmin-induced hydrolysis of glycoproteins. Removal of glycoproteins from the matrix was necessary for the maximal digestion rate of elastin and collagen, and plasmin generation by the tumor cell plasminogen activator therefore played a pivotal role in the hydrolysis of all of the matrix components. The elastolytic and collagenolytic activities were localized to the plasma membrane since no matrix digestion occurred unless the tumor cells were grown in direct contact with the connective tissue proteins. These activities were not inhibited by a wide spectrum of protease inhibitors. The degradation of elastin and collagen required active protein synthesis suggesting a relatively short half-life for the degradative enzyme(s). These quantitative studies, in which tumor cells were grown in contact with a complex extracellular matrix possessing some of the characteristics of connective tissue, should have a bearing on tumor cell invasion.

¹ This work was supported by Research Grant CD-18 from the American Cancer Society.

² To whom requests for reprints should be addressed, at the Division of Hematology-Oncology, Childrens Hospital of Los Angeles, 4650 Sunset Boulevard, Los Angeles, Calif. 90027.

Received 12/26/79. Accepted 5/23/80.

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