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Physical Regulations of Cell Interactions and Metabolism in Tumor Microenvironments

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Engineering and Physical Approaches to Cancer

Part of the book series: Current Cancer Research ((CUCR))

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Abstract

Despite the advances in cancer therapeutics over the recent years, cancer remains the second leading cause of death in the United States, with metastasis accounting for over 90% of cancer-associated mortality. Elucidating the process of tumor progression in the primary tumor is important to the understanding of the sequence of events that gives rise to late stage/metastatic cancer. The primary tumor microenvironment (TME) is a dynamic, heterogeneous, and evolving “ecosystem” comprising numerous cell types and noncellular factors that each play a crucial role in driving tumor progression. The focus on tumor heterogeneity was previously centered around aberrant mutations in tumor cells and biochemical signaling between different TME cell types. However, it is now evident that biophysical cues imposed by the TME also play an important role in tumor progression as the physical traits of the tumor undergo drastic changes and exert abnormal physical restraints and forces that consequently hinder the efficacy of tumor therapeutics. Therefore, understanding the causes of biophysical abnormalities of tumors and the functional consequences will be beneficial for developing new therapeutic strategies. More specifically, we focused on the regulation of metabolism (i.e., metabolic reprogramming) as the primary consequence of the biophysical abnormalities in the TME. Metabolic reprogramming is one of the emerging hallmarks of cancer and is an important regulator of cell fate. In this chapter, we describe the interrelationship between tumor–stromal interactions and altered physical cues such as stiffness, solid stress, and shear stress, and how these ultimately regulate cell metabolism within the TME.

Authors Hydari Masuma Begum and Jeong Min Oh have equally contributed to this chapter.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA

    Hydari Masuma Begum, Jeong Min Oh & Keyue Shen

  2. Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA, USA

    Diane S. Kang & Min Yu

  3. Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Min Yu & Keyue Shen

  4. USC Stem Cell, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Keyue Shen

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  1. Hydari Masuma Begum
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Correspondence to Keyue Shen .

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  1. School of Engineering Department of Pathology & Laboratory Medicine Legoretta Cancer Center, Brown University, Providence, RI, USA

    Ian Y. Wong

  2. Department of Molecular Biology, Cell Biology, & Biochemistry, School of Engineering, and Legoretta Cancer Center, Brown University, Providence, RI, USA

    Michelle R. Dawson

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Begum, H.M., Oh, J.M., Kang, D.S., Yu, M., Shen, K. (2023). Physical Regulations of Cell Interactions and Metabolism in Tumor Microenvironments. In: Wong, I.Y., Dawson, M.R. (eds) Engineering and Physical Approaches to Cancer. Current Cancer Research. Springer, Cham. https://doi.org/10.1007/978-3-031-22802-5_5

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