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Effect of Ascorbic Acid on the Resistance of the Extracellular Matrix to Hydrolysis by Tumor Cells¹

Departments of Pediatrics [Y. A. D., P. A. J.] 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

Extracellular matrices produced by cultured rat smooth muscle cells in the presence or absence of ascorbic acid were used as substrates for the human fibrosarcoma cell line HT1080. The matrix elaborated by smooth muscle cells in the presence of ascorbic acid contained glycoproteins, elastin, and collagen, and all of these components were digested by the tumor cells. In contrast, the matrix elaborated in the absence of ascorbic acid which contained glycoproteins and underhydroxylated elastin but no collagen was more resistant to tumor-induced hydrolysis. The underhydroxylated elastin was particularly refractory to the tumor proteases, suggesting that the elastolytic activity produced by HT1080 cells showed a marked preference for the natural substrate containing hydroxyproline. The digestion by HT1080 cells of elastin from living cultures of smooth muscle cells was also retarded if the extracellular proteins were produced under ascorbic acid-deficient conditions. These experiments therefore do not support the notion that connective tissues made under scorbutic conditions are inherently more susceptible to tumor hydrolysis.

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.