title: Multiscale Modeling of Glioblastoma Suggests that the Partial Disruption of Vessel/Cancer Stem Cell Crosstalk Can Promote Tumor Regression Without Increasing Invasiveness.
abstract: In glioblastoma, the crosstalk between vascular endothelial cells (VECs) and glioma stem cells (GSCs) has been shown to enhance tumor growth. We propose a multiscale mathematical model to study this mechanism, explore tumor growth under various initial and microenvironmental conditions, and investigate the effects of blocking this crosstalk.
  
  
  
  We develop a hybrid continuum-discrete model of highly organized vascularized tumors. VEC-GSC crosstalk is modeled via vascular endothelial growth factor (VEGF) production by tumor cells and by secretion of soluble factors by VECs that promote GSC self-renewal and proliferation.
  
  
  
  VEC-GSC crosstalk increases both tumor size and GSC fraction by enhancing GSC activity and neovascular development. VEGF promotes vessel formation, and larger VEGF sources typically increase vessel numbers, which enhances tumor growth and stabilizes the tumor shape. Increasing the initial GSC fraction has a similar effect. Partially disrupting the crosstalk by blocking VEC secretion of GSC promoters reduces tumor size but does not increase invasiveness, which is in contrast to antiangiogenic therapies, which reduce tumor size but may significantly increase tumor invasiveness.
  
  
  
  Multiscale modeling supports the targeting of VEC-GSC crosstalk as a promising approach for cancer therapy.
authors.forename: Huaming
authors.initials: H
authors.lastname: Yan
authors.forename: Monica
authors.initials: M
authors.lastname: Romero-Lopez
authors.forename: Hermann B
authors.initials: HB
authors.lastname: Frieboes
authors.forename: Christopher C W
authors.initials: CC
authors.lastname: Hughes
authors.forename: John S
authors.initials: JS
authors.lastname: Lowengrub
mesh_terms: D000818:Animals; D002450:Cell Communication; D049109:Cell Proliferation; D002470:Cell Survival; D003198:Computer Simulation; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005909:Glioblastoma / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008954:Models, Biological; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology; D009365:Neoplasm Regression, Spontaneous / Q000473:pathology / Q000503:physiopathology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000503:physiopathology*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A