Treatment for
osteosarcoma is problematic because there are no prognostic markers. Diagnosis is primarily limited to cytologic grading.
Oncogenesis alters cell structure therefore osteoblast tissue
matrix proteins (extracellular matrix, cytoskeletal, intermediate filament, and
nuclear matrix proteins), components of the cell substructure, are candidates for
osteosarcoma markers. Structural
proteins of the extracellular matrix, e.g. the
collagens, are useful for diagnosis but not for
tumors that produce little osteoid. To identify principal cellular tissue matrix
proteins that distinguish normal from transformed human osteoblasts, 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 recurrent. The 1-D SDS/PAGE profiles of the major components of the nuclear matrix and intermediate filament fractions from normal osteoblasts did not vary with biopsy site, age, or sex of patients. These profiles included known
cytoskeletal proteins and OB250, a approximately 250 kD
protein(s) observed in the intermediate filament fraction. A loss of
protein bands, including OB250, was observed in the
osteosarcoma cell lines and
tumors. The intermediate and high grade
tumors exhibited nearly identical
protein profiles including potential
tumor-specific
proteins and
collagen, consistent with the presence of intracellular
collagen fibers in
osteosarcoma. A microsequence was obtained for OT25, a novel low molecular weight
protein observed in
osteosarcoma cell lines.
Fibrinogen gamma-chain, a
protein that mediates cell adhesion was recovered from the high grade recurrent
tumor.