Transformation by Rous sarcoma virus induces similar patterns of glycosaminoglycan synthesis in chick embryo skin fibroblasts and vertebral chondroblasts.
Chick embryo skin fibroblasts and vertebral chondroblasts were infected with a temperature-sensitive mutant of Rous sarcoma virus, LA24A, and were grown at permissive (36 degrees C) and nonpermissive (41 degrees C) temperatures. During exponential growth, infected and parallel uninfected cultures were labeled with D-[3H]glucosamine, and newly synthesized glycosaminoglycans were identified by anion exchange chromatography and by selective enzymatic and chemical degradations. Control fibroblasts synthesized low levels of hyaluronic acid (HA), and dermatan sulfate (DS), moderate levels of heparan sulfate (HS), and high levels of chondroitin sulfate (CS). In contrast, control chondroblasts synthesized very low levels of HA and DS, no HS, and very high levels of CS. Following transformation and growth at 36 degrees C, both cell types showed a dramatic increase in HA synthesis and a significant decrease in CS synthesis. In addition, transformed chondroblasts initiated the synthesis of HS and increased their synthesis of DS to levels that matched those of transformed fibroblasts. The CS chains synthesized by control chondroblasts were partially undersulfated, while those synthesized by both normal and transformed fibroblasts were fully sulfated. Upon transformation, chondroblasts grown at 36 degrees C initiated the synthesis of fully sulfated CS chains. Most of the above biosynthetic alterations were completely reversed when infected cells were grown at 41 degrees C, indicating that they were dependent on the transforming gene product of LA24A. Clearly, the profound differences that distinguish normal fibroblasts from normal chondroblasts are lost upon transformation, and these two types of terminally differentiated cells converge toward a common, though not identical, biosynthetic program for glycosaminoglycans.
D000818:Animals; D001358:Avian Sarcoma Viruses; D002356:Cartilage / Q000378:metabolism*; D002472:Cell Transformation, Viral; D002642:Chick Embryo; D002809:Chondroitin Sulfates / Q000032:analysis; D003871:Dermatan Sulfate / Q000032:analysis; D005347:Fibroblasts / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006497:Heparan Sulfate / Q000032:analysis; D006820:Hyaluronic Acid / Q000032:analysis; D001357:Sarcoma, Avian / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*
D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D006820:Hyaluronic Acid