Quantifying the role of angiogenesis in malignant progression of gliomas: In Silico modeling integrates imaging and histology

K.R. Swanson, Russell C. Rockne, E.C. Alvord Jr., Jonathan Claridge, Mark A. Chaplain, Alexander R.A. Anderson

    Research output: Contribution to journalArticlepeer-review

    139 Citations (Scopus)

    Abstract

    Gliomas are uniformly fatal forms of primary brain neoplasms that vary from low- to high-grade (glioblastoma). Whereas low-grade gliomas are weakly angiogenic, glioblastomas are among the most angiogenic tumors. Thus, interactions between glioma cells and their tissue microenvironment may play an important role in aggressive tumor formation and progression. To quantitatively explore how tumor cells interact with their tissue microenvironment, we incorporated the interactions of normoxic glioma cells, hypoxic glioma cells, vascular endothelial cells, diffusible angiogenic factors, and necrosis formation into a first-generation, biologically based mathematical model for glioma growth and invasion. Model simulations quantitatively described the spectrum of in vivo dynamics of gliomas visualized with medical imaging. Furthermore, we investigated how proliferation and dispersal of glioma cells combine to induce increasing degrees of cellularity, mitoses, hypoxia-induced neoangiogenesis and necrosis, features that characterize increasing degrees of "malignancy," and we found that changes in the net rates of proliferation (?) and invasion (D) are not always necessary for malignant progression. Thus, although other factors, including the accumulation of genetic mutations, can change cellular phenotype (e.g., proliferation and invasion rates), this study suggests that these are not required for malignant progression. Simulated results are placed in the context of the current clinical World Health Organization grading scheme for studying specific patient examples. This study suggests that through the application of the proposed model for tumor-microenvironment interactions, predictable patterns of dynamic changes in glioma histology distinct from changes in cellular phenotype (e.g., proliferation and invasion rates) may be identified, thus providing a powerful clinical tool.
    Original languageEnglish
    Pages (from-to)7366-7375
    Number of pages10
    JournalCancer Research
    Volume71
    Issue number24
    Early online date7 Sep 2011
    DOIs
    Publication statusPublished - 2011

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