MMP-9-hemopexin domain hampers adhesion and migration of colorectal cancer cells

  • Authors:
    • M. Burg-Roderfeld
    • M. Roderfeld
    • S. Wagner
    • C. Henkel
    • J. Grötzinger
    • E. Roeb
  • View Affiliations

  • Published online on: April 1, 2007     https://doi.org/10.3892/ijo.30.4.985
  • Pages: 985-992
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Abstract

atrix metalloproteinases (MMPs), in particular MMP-2 and MMP-9, are involved in colon cancer progression and metastasis due to their ability to degrade extracellular matrix (ECM) components. In previous studies we described the MMP-9 hemopexin like domain (MMP-9-PEX) as an MMP-9 antagonist. In the present study it was examined whether recombinant MMP-9-PEX has an inhibitory effect on migration and adhesion of colorectal carcinoma cells. Furthermore, we searched for MMP-9 substrate binding sites within the MMP-9-PEX by surface plasmon resonance. Migration of SW620 and LS174 cells was investigated in a modified Boyden chamber assay. In the presence of 0.2 µg/ml MMP-9-PEX migration of SW620 was decreased by 34%, while addition of 0.4 µg/ml diminished migration by 56%. Migration of LS174 cells was not affected by MMP-9-PEX. Adhesion studies were performed on 96-well plates coated with gelatin, collagen type I, and laminin, respectively. In the presence of MMP-9-PEX, adhesion of SW620 cells to these coating substrates was significantly inhibited. Surface plasmon resonance studies revealed binding of collagen type I and IV, elastin, and fibrinogen to proMMP-9 as well as to MMP-9-PEX. However, equilibrium constants (Kd) indicated a higher affinity of proMMP-9 to the matrix proteins. This could indicate that there is more than one binding site for matrix components within the entire proMMP-9 molecule. Since migration and adhesion of metastatic colorectal carcinoma cells were reduced by MMP-9-PEX, this recombinant MMP-9 antagonist might be of therapeutical interest.

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April 2007
Volume 30 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Burg-Roderfeld, M., Roderfeld, M., Wagner, S., Henkel, C., Grötzinger, J., & Roeb, E. (2007). MMP-9-hemopexin domain hampers adhesion and migration of colorectal cancer cells. International Journal of Oncology, 30, 985-992. https://doi.org/10.3892/ijo.30.4.985
MLA
Burg-Roderfeld, M., Roderfeld, M., Wagner, S., Henkel, C., Grötzinger, J., Roeb, E."MMP-9-hemopexin domain hampers adhesion and migration of colorectal cancer cells". International Journal of Oncology 30.4 (2007): 985-992.
Chicago
Burg-Roderfeld, M., Roderfeld, M., Wagner, S., Henkel, C., Grötzinger, J., Roeb, E."MMP-9-hemopexin domain hampers adhesion and migration of colorectal cancer cells". International Journal of Oncology 30, no. 4 (2007): 985-992. https://doi.org/10.3892/ijo.30.4.985