Fractal Dimension of Breast Cancer Cell Migration in a Wound Healing Assay
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.
[1] 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.
[2] 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.
[3] 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.
[4] 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
[5] 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.
[6] 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.
[7] 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.
[8] 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.
[9] 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/
[1] 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.
[2] 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.
[3] 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.
[4] 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
[5] 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.
[6] 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.
[7] 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.
[8] 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.
[9] 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/
@article{"International Journal of Biological, Life and Agricultural Sciences:53905", author = "R. Sullivan and T. Holden and G. Tremberger and Jr and E. Cheung and C. Branch and J. Burrero and G. Surpris and S. Quintana and A. Rameau and N. Gadura and H. Yao and R. Subramaniam and P. Schneider and S. A. Rotenberg and P. Marchese and A. Flamhlolz and D. Lieberman and T. Cheung", title = "Fractal Dimension of Breast Cancer Cell Migration in a Wound Healing Assay", abstract = "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.", keywords = "Higuchi fractal dimension, box-counting fractal dimension, cancer cell migration, wound healing.", volume = "2", number = "8", pages = "161-6", }