Mechanical Forces in Tumor Angiogenesis

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1092)


A defining hallmark of cancer and cancer development is upregulated angiogenesis. The vasculature formed in tumors is structurally abnormal, not organized in the conventional hierarchical arrangement, and more permeable than normal vasculature. These features contribute to leaky, tortuous, and dilated blood vessels, which act to create heterogeneous blood flow, compression of vessels, and elevated interstitial fluid pressure. As such, abnormalities in the tumor vasculature not only affect the delivery of nutrients and oxygen to the tumor, but also contribute to creating an abnormal tumor microenvironment that further promotes tumorigenesis. The role of chemical signaling events in mediating tumor angiogenesis has been well researched; however, the relative contribution of physical cues and mechanical regulation of tumor angiogenesis is less understood. Growing research indicates that the physical microenvironment plays a significant role in tumor progression and promoting abnormal tumor vasculature. Here, we review how mechanical cues found in the tumor microenvironment promote aberrant tumor angiogenesis. Specifically, we discuss the influence of matrix stiffness and mechanical stresses in tumor tissue on tumor vasculature, as well as the mechanosensory pathways utilized by endothelial cells to respond to the physical cues found in the tumor microenvironment. We also discuss the impact of the resulting aberrant tumor vasculature on tumor progression and therapeutic treatment.


VE-cadherin VEGF Matrix stiffness MMP Contractility Fluid shear stress Interstitial pressure Mechanotransduction Mechanosensitivity Barrier function 



The authors gratefully acknowledge support from the National Heart, Lung, and Blood Institute (HL127499) to CAR-K and a National Science Foundation Graduate Research Fellowship under Grant No. DGE-1650441 to MRZ.


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Nancy E. and Peter C. Meinig School of Biomedical EngineeringCornell UniversityIthacaUSA
  2. 2.Department of Biomedical EngineeringVanderbilt UniversityNashvilleUSA
  3. 3.Meinig School of Biomedical EngineeringCornell UniversityIthacaUSA

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