Defining rules for cancer cell proliferation in TRAIL stimulation

Page view(s)
20
Checked on Oct 01, 2024
Defining rules for cancer cell proliferation in TRAIL stimulation
Title:
Defining rules for cancer cell proliferation in TRAIL stimulation
Journal Title:
NPJ Systems Biology and Applications
Publication Date:
15 February 2019
Citation:
Deveaux, W., Hayashi, K. & Selvarajoo, K. Defining rules for cancer cell proliferation in TRAIL stimulation. npj Syst Biol Appl 5, 5 (2019). https://doi.org/10.1038/s41540-019-0084-5
Abstract:
Owing to their self-organizing evolutionary plasticity, cancers remain evasive to modern treatment strategies. Previously, for sensitizing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistant human fibrosarcoma (HT1080), we developed and validated a dynamic computational model that showed the inhibition of protein kinase (PK)C, using bisindolylmaleimide (BIS) I, enhances apoptosis with 95% cell death. Although promising, the long-term effect of remaining ~ 5% cells is a mystery. Will they remain unchanged or are they able to proliferate? To address this question, here we adopted a discrete spatiotemporal cellular automata model utilizing simple rules modified from the famous “Conway’s game of life”. Based on three experimental initializations: cell numbers obtained from untreated (high), treatment with TRAIL only (moderate), and treatment with TRAIL and BIS I (low), the simulations show cell proliferation in time and space. Notably, when all cells are fixed in their initial space, the proliferation is rapid for high and moderate cell numbers, however, slow and steady for low number of cells. However, when mesenchymal-like random movement was introduced, the proliferation becomes significant even for low cell numbers. Experimental verification showed high proportion of mesenchymal cells in TRAIL and BIS I treatment compared with untreated or TRAIL only treatment. In agreement with the model with cell movement, we observed rapid proliferation of the remnant cells in TRAIL and BIS I treatment over time. Hence, our work highlights the importance of mesenchymal-like cellular movement for cancer proliferation. Nevertheless, re-treatment of TRAIL and BIS I on proliferating cancers is still largely effective.
License type:
http://creativecommons.org/licenses/by-nd/4.0/
Funding Info:
This work was supported partly by the Japan Society for the Promotion of Science (JSPS), Grants-in-Aid for Scientific Research FX132008K3 (Kumar Selvarajoo), and partly by IAF-PP research fund of the Biotransformation Innovation Platform (BioTrans), Agency for Science, Technology & Research (A*STAR), Singapore. BioTrans IAF-PP
Description:
Open Access Journal: https://www.nature.com/articles/s41540-019-0084-5
ISSN:
2056-7189
Files uploaded:
File Size Format Action
There are no attached files.