Chemotaxis Model for Breast Cancer Cells Based on Signal/Noise Ratio

Cited 7 time in webofscience Cited 0 time in scopus
  • Hit : 248
  • Download : 0
Chemotaxis, a biased migration of cells under a chemical gradient, plays a significant role in diverse biological phenomena including cancer metastasis. Stromal cells release signaling proteins to induce chemotaxis, which leads to organ-specific metastasis. Epidermal growth factor (EGF) is an example of the chemical attractants, and its gradient stimulates metastasis of breast cancer cells. Hence, the interactions between EGF and breast cancer cells have long been a subject of interest for oncologists and clinicians. However, most current approaches do not systematically separate the effects of gradient and absolute concentration of EGF on chemotaxis of breast cancer cells. In this work, we develop a theoretical model based on signal/noise ratio to represent stochastic properties and report our microfluidic experiments to verify the analytical predictions from the model. The results demonstrate that even under the same EGF concentration gradients (0-50 or 0-150 ng/mL), breast cancer cells reveal a more evident chemotaxis pattern when the absolute EGF concentrations are low. Moreover, we found that reducing the number of EGF receptors (EGFRs) with addition of EGFR antibody (1 ng/mL) can promote chemotaxis at an EGF gradient of 0-1 ng/mL as shown by chemotaxis index (0.121 +/- 0.037, reduced EGFRs vs. 0.003 +/- 0.041, control). This counterintuitive finding suggests that EGFR-targeted therapy may stimulate metastasis of breast cancer because the partial suppression of the receptors makes the number of receptors close to the optimal one for chemotaxis. This analysis should be considered in anticancer drug design.
Publisher
CELL PRESS
Issue Date
2018-11
Language
English
Article Type
Article
Citation

BIOPHYSICAL JOURNAL, v.115, no.10, pp.2034 - 2043

ISSN
0006-3495
DOI
10.1016/j.bpj.2018.09.028
URI
http://hdl.handle.net/10203/248275
Appears in Collection
ME-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 7 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0