New aspects of cell biology in osteosarcoma.
Among the solid tumors of childhood and adolescence, osteosarcoma (OS) represents the most prominent example of efficient aggressive chemotherapy with secondary surgical therapy. A specific subclassification of the tumor is indispensable and must include recent results of cell biology. The co-distribution of different collagen types I-VI reflects the diverse differentiation of osteosarcoma cells, supporting the concept of a pluripotent mesenchymal cell to be the stem cell of the tumor. In contrast, osteonectin (SPARC) may not be considered as a reliable marker for osteosarcoma. The experience of special proteins being secreted by osteosarcoma cells is rather limited. Detailed molecular biological studies are still lacking. A loss of alleles on chromosome 17, particularly in the defined region 17p 13, can be observed in more than 75% of all OS, suggesting the contribution of a tumor suppressor gene, p53, located in that region. It is a 53 kd nucleophosphoprotein binding the major transforming protein, the large T antigen of Simian Virus 40. Immunohistological results showed positive staining with the antibody Pab 240 in 13 of 18 cases. In one osteoblastic OS, a novel splice mutation resulting in a fusing of exon 5 directly to exon 7 was detected. RB1 gene is also of major importance for the tumorigenesis of OS. The multidrug resistance (mdr) is associated with a membrane-bound channel-forming transport protein, the P-glycoprotein. It is a conserved plasma membrane component of about 170 kd. Both the human isoforms mdr 1 and mdr 3 are localised in the long arm of chromosome 7.(ABSTRACT TRUNCATED AT 250 WORDS)
D001859:Bone Neoplasms / Q000737:chemistry* / Q000145:classification / Q000188:drug therapy / Q000235:genetics*; D018432:Drug Resistance, Multiple; D016326:Extracellular Matrix Proteins / Q000032:analysis*; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006801:Humans; D009363:Neoplasm Proteins / Q000032:analysis*; D009857:Oncogenes / Q000235:genetics; D012516:Osteosarcoma / Q000737:chemistry* / Q000145:classification / Q000188:drug therapy / Q000235:genetics*
D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins