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Biomechanics in Oncology pp 57–67Cite as

Extracellular Matrix Stiffness Exists in a Feedback Loop that Drives Tumor Progression

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

Abstract

Cells communicate constantly with their surrounding extracellular matrix (ECM) to maintain homeostasis, using both mechanical and chemical signals. In cancer, abnormal signaling leads to stiffening of the ECM. A stiff microenvironment affects many aspects of the cell, including internal molecular signaling as well as behaviors such as motility and proliferation. Thus, cells and ECM interact in a feedback loop to drive matrix deposition and cross-linking, which alter the mechanical properties of the tissue. Stiffer tissue enhances the invasive potential of a tumor and decreases therapeutic efficacy. This chapter describes how specific molecular effects caused by an abnormally stiff tissue drive macroscopic changes that help determine disease outcome. A complete understanding may foster the generation of new cancer therapies.

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Abbreviations

ADAM:

A disintegrin and metalloproteinase

ADAMTS:

ADAMs with thrombospondin motifs

BM:

Basement membrane

CAM:

Chorioallantoic membrane

CB:

Cajal body

CSC:

Cancer stem cell

ECM:

Extracellular matrix

EMT:

Epithelial-mesenchymal transition

FAP:

Fibroblast activation protein

HIF:

Hypoxia-inducible factor

IFP:

Interstitial fluid pressure

ILK:

Integrin-linked kinase

LINC:

Linker of nucleoskeleton and cytoskeleton

MMP:

Matrix metalloproteinase

MRTF:

Myocardin-related transcription factor

MSC:

Mesenchymal stem cell

PTEN:

Phosphatase and tensin homologue

ROCK:

Rho-associated protein kinase

TAZ:

Transcriptional coactivator with PDZ-binding motif

TGF:

Transforming growth factor

TIMP:

Tissue inhibitor of MMP

VEGF:

Vascular endothelial growth factor

YAP:

Yes-associated protein

5FU:

Fluorouracil

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Authors and Affiliations

  1. Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, USA

    Allison K. Simi, Mei-Fong Pang & Celeste M. Nelson

  2. Department of Molecular Biology, Princeton University, Princeton, NJ, USA

    Mei-Fong Pang & Celeste M. Nelson

Authors
  1. Allison K. Simi
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  2. Mei-Fong Pang
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  3. Celeste M. Nelson
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Correspondence to Celeste M. Nelson .

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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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Simi, A.K., Pang, MF., Nelson, C.M. (2018). Extracellular Matrix Stiffness Exists in a Feedback Loop that Drives Tumor Progression. 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_4

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