Export file:


  • RIS(for EndNote,Reference Manager,ProCite)
  • BibTex
  • Text


  • Citation Only
  • Citation and Abstract

Synergistic effect of blocking cancer cell invasionrevealed by computer simulations

1. Division of Mathematical Oncology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai Minato-ku, Tokyo, 108-8639

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 decrease in the efficacy of ECM degradation. Our simulation study suggests the importance of combined strategy in blocking cancer invasion and metastasis.
  Article Metrics

Keywords invasion; MT1-MMP; therapeutic targets.; MMP-2; Cancer

Citation: Kazuhisa Ichikawa. Synergistic effect of blocking cancer cell invasionrevealed by computer simulations. Mathematical Biosciences and Engineering, 2015, 12(6): 1189-1202. doi: 10.3934/mbe.2015.12.1189


  • 1. Cancer Res, 66 (2006), 3034-3043.
  • 2. Cancer Res, 61 (2001), 3610-3618.
  • 3. NatRevCancer, 2 (2002), 161-174.
  • 4. PLoS Comput Biol, 8 (2012), e1002479.
  • 5. Bioinformatics, 17 (2001), 483-484.
  • 6. Neuroinformatics, 3 (2005), 49-64.
  • 7. Oncogene, 31 (2012), 480-493.
  • 8. Cardiovasc Res, 69 (2006), 562-573.
  • 9. MolCancer Ther, 4 (2005), 1157-1166.
  • 10. J Cell Biol, 189 (2010), 541-556.
  • 11. Cancer Res, 67 (2007), 4311-4319.
  • 12. PLoS Comput Biol, 9 (2013), e1003086.
  • 13. ClinExpMetastasis, 23 (2006), 97-105.


This article has been cited by

  • 1. Siti Harun, Daud Israf, Chau Tham, Kok Lam, Manraj Cheema, Nur Md Hashim, The Molecular Targets and Anti-Invasive Effects of 2,6-bis-(4-hydroxyl-3methoxybenzylidine) cyclohexanone or BHMC in MDA-MB-231 Human Breast Cancer Cells, Molecules, 2018, 23, 4, 865, 10.3390/molecules23040865
  • 2. Summer Xia, 心理学进展 (Advances in Psychology), SSRN Electronic Journal, 2012, 10.2139/ssrn.2139207
  • 3. Xianglian Tang, Yong Li, Ming Li, Yuxiang Zhou, Jiabing Wen, Zhao Huang, Yaling Xiao, The role of long noncoding RNAs in regulating invasion and metastasis of malignant tumors, Anti-Cancer Drugs, 2020, 31, 4, 319, 10.1097/CAD.0000000000000899

Reader Comments

your name: *   your email: *  

Copyright Info: 2015, Kazuhisa Ichikawa, licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

Download full text in PDF

Export Citation

Copyright © AIMS Press All Rights Reserved