EPIDERMAL GROWTH-FACTOR RECEPTOR AND INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR EXPRESSION AND FUNCTION IN HUMAN SOFT-TISSUE SARCOMA-CELLS

Epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) receptors are implicated in the development and progression of severa l malignancies including osteogenic and soft tissue sarcomas (STS). To determine a role for ligand-mediated receptor activation in sarcoma p rogression, the relative expression and function of EGF-R, IGF-I-R, an d several other molecular determinants implicated in the progression o f mesenchymal neoplasms were evaluated in human sarcoma cells establis hed from surgical specimens of primary and metastatic tumors. mRNA blo t analyses demonstrated the expression of c-Met, p53, and MDM2-specifi c transcripts. Western blot analyses confirmed the production of high levels of p53 protein; however, minimal levels of MDM2 and c-Met prote ins were detected. Analysis of STS cells #23, #26, and #50 originating from an unclassified sarcoma lung metastasis, a malignant fibrous his tiocytoma lung metastasis, and a dedifferentiated chondrosarcoma, resp ectively demonstrated high steady-state levels of EGF-R and IGF-I-R mR NA transcripts and protein correlating with receptor-specific tyrosine kinase activity and autophosphorylation in response to ligand. Treatm ent of these STS cells with EGF resulted in a >5 fold increase in DNA synthesis and mitogenesis compared with untreated controls. In contras t, treatment with IGF-I showed a variable STS growth response correlat ing with the origin of the tumor. These data support the involvement o f EGF-R and IGF-I-R in the growth and metastasis of human soft tissue sarcoma and may offer new targets for therapeutic intervention in the management of this disease.