Regulation of Tumor Invasion by Cartilage-Derived Anti-Invasion Factor In Vitro23

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Abstract
The resistance of cartilage to tumor invasion was studied with the use of a novel in vitro culture system. Articular cartilage obtained from fresh metacarpophaiangeal joints of pre-adolescent bovines was used as a growth surface for human TE-85 osteosarcoma cells and foreskin fibroblasts. Cartilage disks formed the bottoms of stainless-steel cylinders, providing closed growth chambers for these cells. Both invasive osteosarcoma cells and normal fibroblasts were unable to penetrate viable, unextracted cartilage during a 2-week culture period. When cartilage was devitalized by freezing and thawing, the tissue remained resistant to invasion. Cartilage, extracted with either 1 or 3 M guanidine hydrochloride, was invaded by osteosarcoma cells, but not by control fibroblasts. Invasion by osteosarcoma cells into salt-extracted cartilage was abolished when low concentrations of a cartilage-derived, anti-invasion factor were added to the culture medium. These data provided evidence that the resistance of cartilage to tumor invasion is regulated in part by tissue-derived proteinase inhibitors.