heparitin-sulfate and motretinide

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.

Topics: Animals; Chondrosarcoma; Glycosaminoglycans; Heparitin Sulfate; Male; Proteoglycans; Rats; Sarcoma, Experimental; Tretinoin