Synergistic effect of blocking cancer cell invasion revealed by computer simulations

Mathematical Biosciences and Engineering : MBE
Kazuhisa Ichikawa

Abstract

Invasion and metastasis are the main cause of death in cancer patients. The initial step of invasion is the degradation of extracellular matrix (ECM) by primary cancer cells in a tissue. Membranous metalloproteinase MT1-MMP and soluble metalloproteinase MMP-2 are thought to play an important role in the degradation of ECM. In the previous report, we found that the repetitive insertion of MT1-MMP to invadopodia was crucial for the effective degradation of ECM (Hoshino, D., et al., PLoS Comp. Biol., 2012, e1002479). However, the role of MMP-2 and the effect of inhibitors for these ECM-degrading proteases were still obscure. Here we investigated these two problems by using the same model as in the previous report. First we tested the effect of MMP-2 and found that while MT1-MMP played a major role in the degradation of ECM, MMP-2 played only a marginal effect on the degradation of ECM. Based on these findings, we next tested the effect of a putative inhibitor for MT1-MMP and found that such inhibitor was ineffective in blocking ECM degradation. Then we tested combined strategy including inhibitor for MT1-MMP, reduction of its turnover and its content in vesicles. A synergistic effect of combined strategy was observed in the decrea...Continue Reading

References

May 7, 2002·Nature Reviews. Cancer·Mikala Egeblad, Zena Werb
Jan 13, 2006·Cardiovascular Research·Hideaki NagaseGillian Murphy
Jul 11, 2006·Clinical & Experimental Metastasis·Alissa M Weaver
Apr 28, 2010·The Journal of Cell Biology·Marie SchoumacherDanijela M Vignjevic

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Citations

Apr 13, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Siti Nor Aini HarunNur Fariesha Md Hashim
Jan 1, 2021·Frontiers in Cellular and Infection Microbiology·Ana Claudia TorrecilhasMartin Olivier

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