Effect of the retinoic acid analog Ro 11-1430 on proteoglycans of swarm rat chondrosarcoma.
When treated with a retinoic acid analog (Ro 11-1430), the Swarm rat chondrosarcoma regressed (t 1/2 = 11-12 days) with a rapid removal of tumor proteoglycan, histologic evidence of mineralization, and cartilage proteoglycan synthesis was suppressed down to a value of 1% of the control. During the first 3 weeks of treatment, the newly synthesized proteoglycan was similar both in aggregation and size to the proteoglycan present in the control. However, after 5 weeks of treatment synthesis shifted to a small nonaggregating proteoglycan with longer glycosaminoglycan chains now containing dermatan sulfate, possibly representing a switch in proteoglycan synthesized. Heparan sulfate was also detected. Unlabeled proteoglycan released from the tissue during Ro 11-1430 treatment was large (Kav = 0.25 on Sepharose CL-2B) but incapable of aggregation, suggesting the initial proteolytic cleavage was in or near the hyaluronic acid-binding region of the proteoglycan. Degradative enzyme activity varied during the period of treatment. Since other tissues remained histologically normal during the treatment with Ro 11-1430, this drug may have possible therapeutic value.
D000818:Animals; D002813:Chondrosarcoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006025:Glycosaminoglycans / Q000032:analysis; D006497:Heparan Sulfate / Q000032:analysis; D008297:Male; D011509:Proteoglycans / Q000032:analysis*; D051381:Rats; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000494:pharmacology
D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D011509:Proteoglycans; D014212:Tretinoin; C010832:motretinide