Mathematical modelling of the role of Endo180 network in the development of metastatic bone disease in prostate cancer. (February 2020)

• Record Type: Journal Article
• Authors: Ji, Bing; Chen, Jie; Zhen, Changqing; Yang, Qing; Yu, Nengwang
• Is Part Of: Computers in biology and medicine. Volume 117(2020)
• Publication Date: 2020-02
• Subjects: Bone remodelling -- Mathematical model -- Endo180 -- MBD; Medicine -- Data processing -- Periodicals; Biology -- Data processing -- Periodicals; 610.285
• DOI: 10.1016/j.compbiomed.2020.103619
• Languages: English
• ISSNs: 0010-4825

Abstract

Abstract: Metastatic bone disease (MBD) is a common complication of advanced cancer and recent research suggests that Endo180 expression is dysregulated through the TGFβ-TGFβR-SMAD2/3 signalling pathway during the invasion of tumour cells in the development of MBD. We here provide a model for the dysregulation of the Endo180 network to demonstrate its vital contribution to bone destruction as well as tumour cell growth. The model consisted of a set of ordinary differential equations and reconstructed variations in the bone cells, resultant bone volume, and biochemical factors involved in the TGFβ-TGFβR-SMAD2/3 signalling pathway over time. The model also investigated the underlying mechanism in which the change of TGFβ affects the TGFβ-TGFβR-SMAD2/3 signalling pathway and the resultant Endo180 expression in osteoblastic and tumour cells. The model links the appearance of tumour cells with the inhibition of TGFβ binding to its receptors on osteoblastic cells, to affect TGFβ-TGFβR-SMAD2/3 signalling and Endo180 expression. Temporal variation in bone cells, bone volume, and the biochemical factors involved in the TGFβ-TGFβR-SMAD2/3 pathway as demonstrated in the model simulations agree with published experimental data. The model can be refined based on further discoveries but allows the influence of Endo180 network dysregulation on bone remodelling in MBD to be established. This model could aid in the development of Endo180 targeted therapies for MBD in the future. Graphical abstract: An extended mathematical model of MBD is proposed in this paper that includes the mechanism of how Endo180 dysregulation facilitates the survival of tumour cells in the bone microenvironment and further destroys bone function. The model consisted of a set of ordinary differential equations and reconstructed variations in the bone cells, resultant bone volume, and biochemical factors involved in the TGFβ-TGFβR-SMAD2/3 signalling pathway over time. Image 1 Highlights: A mathematical model was constructed to mimic the development of metastatic bone disease with the inclusion of Endo180. The model can investigate the underlying mechanism in which the change of TGFβ affects the TGFβ-TGFβR-SMAD2/3 pathway. The model can simulate TGFβ variation influences the resultant Endo180 expression in osteoblastic and tumour cells.