Expression of the extracellular matrix molecule thrombospondin inversely correlates with malignant progression in melanoma, lung and breast carcinoma cell lines

Int J Cancer. 1994 Oct 15;59(2):191-5. doi: 10.1002/ijc.2910590209.


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.

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cell Adhesion Molecules / biosynthesis*
  • Cell Adhesion Molecules / genetics
  • DNA Probes
  • Gene Expression
  • Genes, ras
  • Humans
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Melanoma / pathology*
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / genetics
  • Mice
  • Models, Biological
  • Monomeric GTP-Binding Proteins*
  • NM23 Nucleoside Diphosphate Kinases
  • Nucleoside-Diphosphate Kinase*
  • Thrombospondins
  • Transcription Factors / genetics
  • Transfection
  • Tumor Cells, Cultured


  • Cell Adhesion Molecules
  • DNA Probes
  • Membrane Glycoproteins
  • NM23 Nucleoside Diphosphate Kinases
  • Thrombospondins
  • Transcription Factors
  • NME1 protein, human
  • Nme1 protein, mouse
  • Nucleoside-Diphosphate Kinase
  • Monomeric GTP-Binding Proteins