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 chemoth erapy with secondary surgical therapy. A specific subclassification of the tumor is indispensable and must include recent results of cell bi ology. The co-distribution of different collagen types I-VI reflects t he diverse differentiation of osteosarcoma cells, supporting the conce pt 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 secr eted by osteosarcoma cells is rather limited Detailed molecular biolog ical studies are still lacking. A loss of alleles on chromosome 17, pa rticularly 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 bindi ng the major transforming protein, the large T antigen of Simian Virus 40. Immunohistological results showed positive staining with the anti body 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 teas dete cted. RBI gene is also of major importance for the tumorigenesis of OS . The multidrug resistance (mdr) is associated with a membrane-bound c hannel-forming transport protein, the P-glycoprotein. It is a conserve d plasma membrane component of about 170 kd. Both the human isoforms m dr 1 and mdr 3 are localised in the long arm of chromosome 7. A statis tically significant correlation between P-glycoprotein expression and response to chemotherapy for OS could not be, as of now, fully establi shed.