title: Modeling Proteolytically Driven Tumor Lymphangiogenesis.
abstract: With the exception of a limited number of sites in the body, primary tumors infrequently lead to the demise of cancer patients. Instead, mortality and a significant degree of morbidity result from the growth of secondary tumors in distant organs. Tumor survival, growth and dissemination are associated with the formation of both new blood vessels (angiogenesis) and new lymph vessels (lymphagenesis or lymphangiogenesis). Although intensive research in tumor angiogenesis has been going on for the past four decades, experimental results in tumor lymphangiogenesis began to appear only in the last 10 years. In this chapter we expand the models proposed by Friedman, Lolas and Pepper on tumor lymphangiogenesis mediated by proteolytically and un-proteolytically processed growth factors (Friedman and Lolas G, Math Models Methods Appl Sci 15(01):95-107, 2005; Pepper and Lolas G, Selected topics in cancer modeling: genesis, evolution, immune competition, and therapy. In: The lymphatic vascular system in lymphangiogenesis invasion and metastasis a mathematical approach. Birkhäuser Boston, Boston, pp 1-22, 2008). The variables represent different cell densities and growth factors concentrations, and where possible the parameters are estimated from experimental and clinical data. The results obtained from computational simulations carried out on the model equations produce dynamic heterogeneous ("anarchic") spatio-temporal solutions. More specifically, we observed coherent masses of tumor clusters migrating around and within the lymphatic network. Our findings are in line with recent experimental evidence that associate cluster formation with the minimization of cell loss favoring high local extracellular matrix proteolysis and thus protecting cancer invading cells from an immunological assault driven by the lymphatic network.
authors.affiliation: Oncology Unit, 3rd Department of Internal Medicine, Sotiria General Hospital, Athens School of Medicine, Athens, Greece. glolas@med.uoa.gr.
authors.forename: Georgios
authors.initials: G
authors.lastname: Lolas
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), C1, Karolinska Institute, Stockholm, Sweden.|Department of Medical and Health Sciences, Linköping University, 581 85, Linköping, Sweden.
authors.forename: Lasse
authors.initials: L
authors.lastname: Jensen
authors.affiliation: Faculty of Science, Technology and Communication, University of Luxembourg, Campus Kirchberg, 6,rue Richard Coudenhove-Kalergi L-1359, Luxembourg City, Luxembourg.
authors.forename: George C
authors.initials: GC
authors.lastname: Bourantas
authors.affiliation: Oncology Unit, 3rd Department of Internal Medicine, Sotiria General Hospital, Athens School of Medicine, Athens, Greece.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Tsikourkitoudi
authors.affiliation: Oncology Unit, 3rd Department of Internal Medicine, Sotiria General Hospital, Athens School of Medicine, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Syrigos
mesh_terms: D000818:Animals; D002465:Cell Movement; D003198:Computer Simulation; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D015233:Models, Statistical; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D059748:Proteolysis; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism
chemical_list: C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C
keywords: Lymphangiogenesis; Mature VEGF-C; Plasmin; Proteolysis; Tumor clusters; Tumor heterogeneity