TISSUE MATRIX PROTEIN EXPRESSION IN HUMAN OSTEOBLASTS, OSTEOSARCOMA TUMORS, AND OSTEOSARCOMA CELL-LINES

Treatment for osteosarcoma is problematic because there are no prognos tic markers. Diagnosis is primarily limited to cytologic grading. Onco genesis alters cell structure therefore osteoblast tissue matrix prote ins (extracellular matrix, cytoskeletal, intermediate filament, and nu clear matrix proteins), components of the cell substructure, are candi dates for osteosarcoma markers. Structural proteins of the extracellul ar matrix, e.g. the collagens, are useful for diagnosis but not for tu mors that produce little osteoid. To identify principal cellular tissu e matrix proteins that distinguish normal from transformed human osteo blasts, their expression in normal osteoblasts, two osteosarcoma cell lines, and three primary osteosarcoma tumors were compared. The tumors were graded as (i) intermediate, (ii) high, and (iii) high grade recu rrent. The 1-D SDS/PAGE profiles of the major components of the nuclea r matrix and intermediate filament fractions from normal osteoblasts d id not vary with biopsy site, age, or sex of patients. These profiles included known cytoskeletal proteins and OB250, a similar to 250 kD pr otein(s) observed in the intermediate filament fraction. A loss of pro tein bands, including OB250, was observed in the osteosarcoma cell lin es and tumors. The intermediate and high de tumors exhibited nearly id entical protein profiles including potential tumor-specific proteins a nd collagen, consistent with the presence of intracellular collagen fi bers in osteosarcoma. A microsequence was obtained for OT25. a novel l ow molecular weight protein observed in osteosarcoma cell lines. Fibri nogen gamma-chain, a protein that mediates cell adhesion was recovered from the high grade recurrent tumor.