Modulation of type-iv collagenase activity and invasive behavior of metastatic human melanoma (A2058) cells in vitro by monoclonal antibodies to type-iv collagenase

✍ Scribed by Matti Höyhtyä; Erkki Hujanen; Taina Turpeenniemi-Hujanen; Unnur Thorgeirsson; Lance A. Liotta; Karl Tryggvason

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: French
• Weight: 758 KB
• Volume: 46
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910460224

✦ Synopsis

Monoclonal antibodies (MAbs) against human type-IV collagenase were developed and used for studies on enzyme activity and tumor-cell invasion in vitro. Fifteen MAb clones were generated against the enzyme purified from serum-free culture medium of human melanoma cells (A2058). Five clones affecting the activity of type-IV collagenase were selected for further characterization. All the selected clones could be used for a single-step purification of type-IV collagenase using IgG-Sepharose affinity columns. One of the antibodies activated the enzyme when 'H-proline-labelled type-I V collagen was used as substrate. The activation was dependent on the enzyme antibody ratio. Four clones caused more than 30% inhibition of the activity, maximal inhibition being 50%. Interestingly, the same antibody which activated the enzyme also increased the invasion of A2058 cells through a reconstituted basement membrane in an in vitro invasion assay. The 4 inhibitory antibodies decreased the penetration of A2058 cells through the reconstituted basement membrane. The results strongly support previous findings about the importance of type-IV collagenase in tumor-cell invasion.