TY - JOUR
T1 - Glial progenitor cell recruitment drives aggressive glioma growth
T2 - Mathematical and experimental modelling
AU - Massey, Susan Christine
AU - Assanah, Marcela C.
AU - Lopez, Kim A.
AU - Canoll, Peter
AU - Swanson, Kristin R.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2012/8/7
Y1 - 2012/8/7
N2 - Currently available glioma treatments remain unsuccessful at prolonging disease-free remission. Recent evidence suggests that tumour recruitment of glial progenitor cells by platelet-derived growth factor (PDGF) may play a role in the development and progression of these tumours. Building upon our recent experimental results and previous proliferation-invasion (PI) reaction- diffusion model, in this study, we created a proliferation-invasion-recruitment (PIR) model that includes a mechanism for progenitor cell recruitment, wherein paracrine PDGF signalling stimulates migration and proliferation of progenitors derived from the local brain environment. Parametrizing this mathematical model with data obtained from the PDGF-driven rat glioma model, we explored the consequences of recruitment, using the PIR model to compare the effects of high versus low PDGF secretion rates on tumour growth and invasion dynamics. The mathematical model predicts correlation between high levels of recruitment and both increased radial velocity of expansion on magnetic resonance imaging and less diffusely invasive edges. Thus, the PIR model predicts that PDGF levels correlate with tumour aggressiveness, and results are consistent with both human and experimental data, demonstrating that the effects of progenitor cell recruitment provide a novelmechanism to explain the variability in the rates of proliferation and dispersion observed in human gliomas.
AB - Currently available glioma treatments remain unsuccessful at prolonging disease-free remission. Recent evidence suggests that tumour recruitment of glial progenitor cells by platelet-derived growth factor (PDGF) may play a role in the development and progression of these tumours. Building upon our recent experimental results and previous proliferation-invasion (PI) reaction- diffusion model, in this study, we created a proliferation-invasion-recruitment (PIR) model that includes a mechanism for progenitor cell recruitment, wherein paracrine PDGF signalling stimulates migration and proliferation of progenitors derived from the local brain environment. Parametrizing this mathematical model with data obtained from the PDGF-driven rat glioma model, we explored the consequences of recruitment, using the PIR model to compare the effects of high versus low PDGF secretion rates on tumour growth and invasion dynamics. The mathematical model predicts correlation between high levels of recruitment and both increased radial velocity of expansion on magnetic resonance imaging and less diffusely invasive edges. Thus, the PIR model predicts that PDGF levels correlate with tumour aggressiveness, and results are consistent with both human and experimental data, demonstrating that the effects of progenitor cell recruitment provide a novelmechanism to explain the variability in the rates of proliferation and dispersion observed in human gliomas.
KW - Glial progenitors
KW - Glioma
KW - Mathematical modelling
KW - Platelet-derived growth factor
KW - Recruitment
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U2 - 10.1098/rsif.2012.0030
DO - 10.1098/rsif.2012.0030
M3 - Article
C2 - 22319102
AN - SCOPUS:84865080890
VL - 9
SP - 1757
EP - 1766
JO - Journal of the Royal Society Interface
JF - Journal of the Royal Society Interface
SN - 1742-5689
IS - 73
ER -