Angiogenic Signaling and Structural Abnormalities in Tumors
Growing tumor needs to be supplied with oxygen and nutrients; hence, the mechanisms responsible for development of new blood vessels are crucial for tumor progression. Enhanced expression of proangiogenic factors enables development of tumor vasculature a
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Magdalena Tertil, Klaudia Skrzypek, and Agnieszka Łoboda
Contents 17.1 17.2 17.3
Angiogenic Signaling in Tumor Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Stromal Cells in Tumor Angiogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Heterogeneity of Tumor Vasculature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17.3.1 Tumor Vasculature Is Unique . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17.3.2 Alternative Mechanisms of Neovascularization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Abstract
Growing tumor needs to be supplied with oxygen and nutrients; hence, the mechanisms responsible for development of new blood vessels are crucial for tumor progression. Enhanced expression of proangiogenic factors enables development of tumor vasculature and subsequent invasion of tumor cells. The key step in these events is decreased oxygen tension within the growing tumor due to limited oxygen diffusion within the tissue. Apart from canonical hypoxic signaling,
M. Tertil Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krako´w, Poland Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krako´w, Poland K. Skrzypek Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krako´w, Poland Department of Transplantation, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Krako´w, Poland A. Łoboda (*) Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krako´w, Poland e-mail: [email protected] J. Dulak et al. (eds.), Angiogenesis and Vascularisation, DOI 10.1007/978-3-7091-1428-5_17, # Springer-Verlag Wien 2013
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there are numerous molecular pathways that may modulate angiogenic secretome of cancer cells, such as the action of angiogenic enzymes and microRNAs. Besides tumor cells, also other cellular components of tumor microenvironment play an important role in stimulation of endothelium, out of which the key players are different populations of bone marrow-derived cells of myeloid origin. Overstimulation of endothelial cells leads to development of abnormal vasculature that may be further disorganized by adaptation of alternative mechanisms of vascularization such as vessel co-option, intussusceptive microvascular growth or glomeruloid angiogenesis. Several tumor types are also capable of forming functiona
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