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Biomechanics in Oncology pp 91–112Cite as

Mechanical Forces in Tumor Angiogenesis

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

Abstract

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.

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Notes

  1. 1.

    The MMTV-PyMT transgenic mouse model is widely used to study mammary tumor progression and metastasis. In the MMTV-PyMT model, mammary gland-specific expression of the polyoma middle T antigen (PyMT) oncogene driven by the upstream mouse mammary tumor virus (MMTV) long terminal repeat promoter results in mammary epithelium transformation and rapid development of multifocal mammary adenocarcinomas and metastatic lesions.

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Acknowledgments

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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Authors and Affiliations

  1. Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA

    Matthew R. Zanotelli

  2. Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA

    Cynthia A. Reinhart-King

  3. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA

    Cynthia A. Reinhart-King

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  1. Matthew R. Zanotelli
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  2. Cynthia A. Reinhart-King
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Correspondence to Cynthia A. Reinhart-King .

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Editors and Affiliations

  1. Department of Biomedical Engineering, Pennsylvania State University, University Park, PA, USA

    Cheng Dong

  2. Division of Cancer Biology, National Cancer Institute, National Institutes of Health, Rockville, MD, USA

    Nastaran Zahir

  3. Department of Chemical and Biomolecular Engineering Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA

    Konstantinos Konstantopoulos

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Zanotelli, M.R., Reinhart-King, C.A. (2018). Mechanical Forces in Tumor Angiogenesis. In: Dong, C., Zahir, N., Konstantopoulos, K. (eds) Biomechanics in Oncology. Advances in Experimental Medicine and Biology, vol 1092. Springer, Cham. https://doi.org/10.1007/978-3-319-95294-9_6

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