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Biomarkers of the Tumor Microenvironment pp 91–107Cite as

Tissue Architecture in Cancer Initiation and Progression

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Abstract

Tumors that originate from epithelial cells are referred to as carcinomas and represent the most frequently diagnosed cancers. Epithelial tissue is abundant throughout the body, where it lines organs to serve as a protective barrier against biological, chemical, and physical insults. As such, the maintenance of epithelial tissue architecture is critical for tissue homeostasis and healthy tissue functioning. The structure and function of epithelial tissues are largely influenced by the surrounding microenvironment, which is comprised of an acellular interstitial matrix and stromal cells. The makeup and architecture of this surrounding microenvironment are thus key players in cancer suppression, initiation, progression, and metastasis. Over the course of disease progression, the tumor microenvironment undergoes extensive extracellular matrix remodeling, while stromal cells infiltrate and undergo phenotypic switches to mediate tumor-suppressive and tumor-promoting roles. The detection of aberrant extracellular matrix and stromal cell infiltration and activation thus serve as important biomarkers of patient disease and may provide diagnostic and prognostic value. Consequently, a promising avenue for the future of personalized medicine is the development of targeted therapeutics aimed at normalizing the tumor microenvironment.

Carcinomas are malignant tumors that originate from cells in epithelial tissue. There, abnormal epithelial cells grow uncontrollably, breach the basement membrane, undergo cell-state transitions, invade into the underlying interstitial matrix, and subsequently disseminate to form distant metastases. Concomitantly, dramatic alterations of the tissue stroma contribute to the generation of a tumor-promoting microenvironment. Solid stress and interstitial fluid pressure are elevated in tumors, and the interstitial matrix becomes increasingly stiffened and aligned compared to that of healthy tissues. These physical changes are facilitated by dynamic processes, such as angiogenesis and the recruitment and activation of stromal cells. Further, tumor cells, cancer-associated fibroblasts, and tumor-associated macrophages drive matrix remodeling, which aids in the escape of tumor cells from the primary site. Overall, the tumor microenvironment plays a critical role in cancer initiation and progression. Thus, the tumor microenvironment may be viewed as a complex ecosystem that could be exploited to generate unconventional therapeutics for cancer treatment in the future.

Keywords

  • Mechanobiology
  • Mechanical force
  • ECM
  • Tissue morphodynamics

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Fig. 6.1
Fig. 6.2
Fig. 6.3
Fig. 6.4

Abbreviations

CAF:

cancer-associated fibroblast

ECM:

extracellular matrix

EMT:

epithelial-mesenchymal transition

FAP:

fibroblast activation protein

GAG:

glycosaminoglycan

GF:

growth factor

HLA:

hyaluronic acid

IFP:

interstitial fluid pressure

LOX:

lysyl oxidase

MMP:

matrix metalloproteinase

MET:

mesenchymal-epithelial transition

3D:

three-dimensional

TAM:

tumor-associated macrophage

TME:

tumor microenvironment

TGF-β:

transforming growth factor-beta

VEGF:

vascular endothelial growth factor

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Authors and Affiliations

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

    Susan E. Leggett & Celeste M. Nelson

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

    Celeste M. Nelson

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  1. Susan E. Leggett
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  2. Celeste M. Nelson
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Correspondence to Celeste M. Nelson .

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Editors and Affiliations

  1. Centre for Cancer Biomarkers CCBIO Department of Clinical Medicine, University of Bergen, Bergen, Norway

    Lars A. Akslen

  2. Department of Surgery, Harvard Medical School, Vascular Biology Program, Boston Children’s Hospital, Boston, USA

    Randolph S. Watnick

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Leggett, S.E., Nelson, C.M. (2022). Tissue Architecture in Cancer Initiation and Progression. In: Akslen, L.A., Watnick, R.S. (eds) Biomarkers of the Tumor Microenvironment. Springer, Cham. https://doi.org/10.1007/978-3-030-98950-7_6

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  • DOI: https://doi.org/10.1007/978-3-030-98950-7_6

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