Published August 24, 2008 | Version 4794
Journal article Open

Fractal Dimension of Breast Cancer Cell Migration in a Wound Healing Assay

Description

Migration in breast cancer cell wound healing assay had been studied using image fractal dimension analysis. The migration of MDA-MB-231 cells (highly motile) in a wound healing assay was captured using time-lapse phase contrast video microscopy and compared to MDA-MB-468 cell migration (moderately motile). The Higuchi fractal method was used to compute the fractal dimension of the image intensity fluctuation along a single pixel width region parallel to the wound. The near-wound region fractal dimension was found to decrease three times faster in the MDA-MB- 231 cells initially as compared to the less cancerous MDA-MB-468 cells. The inner region fractal dimension was found to be fairly constant for both cell types in time and suggests a wound influence range of about 15 cell layer. The box-counting fractal dimension method was also used to study region of interest (ROI). The MDAMB- 468 ROI area fractal dimension was found to decrease continuously up to 7 hours. The MDA-MB-231 ROI area fractal dimension was found to increase and is consistent with the behavior of a HGF-treated MDA-MB-231 wound healing assay posted in the public domain. A fractal dimension based capacity index has been formulated to quantify the invasiveness of the MDA-MB-231 cells in the perpendicular-to-wound direction. Our results suggest that image intensity fluctuation fractal dimension analysis can be used as a tool to quantify cell migration in terms of cancer severity and treatment responses.

Files

4794.pdf

Files (213.3 kB)

Name Size Download all
md5:5ebdbc6d92ebbd1a1cb473d0d61d252c
213.3 kB Preview Download

Additional details

References

  • Teri L Larkins, Marchele Nowell, Shailesh Singh and Gary L Sanford, "Inhibition of cyclooxygenase-2 decreases breast cancer cell motility, invasion and matrix metalloproteinase expression" BMC Cancer, Vol 6, p181-193, doi:10.1186/1471-2407-6-181, 2006.
  • Gargi D Basu, Latha B Pathangey, Teresa L Tinder, Sandra J Gendler and Pinku Mukherjee, "Mechanisms underlying the growth inhibitory effects of the cyclo-oxygenase-2 inhibitor celecoxib in human breast cancer cells" Breast Cancer Research, Vol. 7, R422-R435, 2005.
  • George Tzircotis, Rick F. Thorne and Clare M. Isacke, "Chemotaxis towards hyaluronan is dependent on CD44 expression and modulated by cell type variation in CD44 hyaluronan binding" Journal of Cell Science Vol. 118, p5119-5128, 2005.
  • Jin Pu, Colin D. McCaig, Lin Cao, Zhiqiang Zhao, Jeffrey E. Segall and Min Zhao, "EGF receptor signalling is essential for electric-field directed migration of breast cancer cells" Journal of Cell Science Vol. 120, p3395-3403, 2007
  • Zoe N. Demou, Michael Awad, Trevor McKee, Jean Yannis Perentes, Xiaoye Wang, Lance L. Munn, Rakesh K. Jain, and Yves Boucher, "Lack of Telopeptides in Fibrillar Collagen I Promotes the Invasion of a Metastatic Breast Tumor Cell Line" Cancer Research Vol. 65: p5674- 5682, 2005.
  • Masahiro Yanagisawa and Panos Z. Anastasiadis, "p120 catenin is essential for mesenchymal cadherin-mediated regulation of cell motility and invasiveness" The Journal of Cell Biology, Vol. 174, p1087-1096, 2006.
  • A. Bru, S. Albertos, J. Subiza, J. Garcia-Asenjo, and I. Bru , "The Universal Dynamics of Tumor Growth" Biophysical Journal, vol-85, 2948-2961, 2003.
  • Allison Pledgie-Tracy, Michele D. Sobolewski, and Nancy E. Davidson, "Sulforaphane induces cell type-specific apoptosis in human breast cancer cell lines" Mol Cancer Ther Vol. 6, p1013-1021, 2007.
  • Liang C. et al., "In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro Nature protocols 2; (http://www.nature.com/nature protocol), 2007. [10] W. Klonowski "From conformons to human brains: an informal overview of nonlinear dynamics and its applications in biomedicine".Nonlinear Biomed Phys. 2007 Jul 5; 1(1):5. [11] T. Higuchi, "Approach to an irregular time series on the basis of fractal theory", Physica D, vol 31, 277-283, 1998. [12] Xinmin Yang, Haluk Beyenal, Gary Harkin, Zbigniew Lewandowski," Quantifying biofilm structure using image analysis", Journal of Microbiological Methods, Vol 39, Pages 109-119, 2000. [13] T. Sungkaworn, W. Triampo, P. Nalakarn, D. Triampo, I. M. Tang, Y. Lenbury, and P. Picha," The Effects of TiO2 Nanoparticles on Tumor Cell Colonies: Fractal Dimension and Morphological Properties" International Journal of Biomedical Sciences Vol. 2, p67-74, 2007. [14] http://mayoresearch.mayo.edu/mayo/research/anastasiadis_lab/cellmigration. cfm (last assessed September 12 2008). [15] E.W. Weisstein, "Capacity Dimension." From MathWorld--A Wolfram Web Resource. http://mathworld.wolfram.com/