Expression of the extracellular matrix molecule thrombospondin inversely correlates with malignant progression in melanoma, lung and breast carcinoma cell lines.
Thrombospondin (TSP) is a member of a family of extracellular matrix glycoproteins that may participate in multiple aspects of the metastatic cascade. We report an inverse correlation of steady-state Thbs-1 mRNA and protein expression with malignant progression among murine melanoma and human lung and breast carcinoma cell lines. Murine K-1735 melanoma cell lines of low metastatic potential, including K-1735 lines transfected with the murine nm23-1 cDNA, expressed higher TSP levels than related highly metastatic lines. In a model system of lung carcinoma malignant progression, immortalized human bronchial epithelial cells expressed higher TSP levels than v-Ki-ras, v-Ha-ras or n-ras transfectants, which in turn expressed higher TSP levels than tumor-derived, more aggressive variants. Among 3 unrelated breast carcinoma cell lines, Thbs-1 steady-state mRNA levels were greater in the 2 non-metastatic lines than the metastatic line. Our data show that malignant progression in some cell lines is associated with reduced TSP expression. The suppressive effects of nm23-1 transfection on metastatic potential are also associated with increased TSP expression; ras transfection, which results in increased tumorigenesis, is associated with decreased TSP expression.
Zabrenetzky
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Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Harris
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CC
Steeg
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Roberts
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DD
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D015342:DNA Probes; D015870:Gene Expression; D011905:Genes, ras; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008954:Models, Biological; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D019699:Thrombospondins; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D015342:DNA Probes; D008562:Membrane Glycoproteins; D054778:NM23 Nucleoside Diphosphate Kinases; D019699:Thrombospondins; D014157:Transcription Factors; C517938:NME1 protein, human; C517939:Nme1 protein, mouse; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins