Coexpression of a PDGF-like growth factor and PDGF receptors in a human osteosarcoma cell line: implications for autocrine receptor activation.
The expression of both a PDGF-like growth factor and functional PDGF receptors within a clonal human osteosarcoma cell line (U-2 OS Cl 6) is demonstrated. These molecules are able to interact and induce tyrosine-specific phosphorylation and early actin reorganization in the osteosarcoma cells, effects similar to those that PDGF induces in normal responsive cells. Furthermore, immunoprecipitation with an antiserum against phosphotyrosine revealed that a 115 kd protein was constitutively phosphorylated in U-2 OS Cl 6 cells. A phosphorylated protein of similar apparent molecular weight has been found in human fibroblasts, but only after stimulation with PDGF. These data indicate that the PDGF-receptor-dependent pathway is constitutively activated in this cell line. Extracellularly added PDGF antibodies did not, however, affect the transformed properties or growth rate of U-2 OS Cl 6 cells in vitro. This indicates that autocrine PDGF receptor activation may be insignificant for maintaining the transformed state of this tumor cell line, or that autocrine receptor activation occurs in a compartment where it is inaccessible to extracellularly added antibodies.
D000906:Antibodies; D000936:Antigen-Antibody Complex; D002460:Cell Line; D004261:DNA Replication; D005347:Fibroblasts / Q000166:cytology; D005455:Fluorescent Antibody Technique; D006801:Humans; D009693:Nucleic Acid Hybridization; D012516:Osteosarcoma / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D011494:Protein Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases; D012334:RNA, Neoplasm / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics*; D017479:Receptors, Platelet-Derived Growth Factor
D000906:Antibodies; D000936:Antigen-Antibody Complex; D010982:Platelet-Derived Growth Factor; D012334:RNA, Neoplasm; D011956:Receptors, Cell Surface; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor