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14 - Role of Inflammation in Metastatic Progression

from STROMAL CELLS/EXTRACELLULAR MATRIX

Published online by Cambridge University Press:  05 June 2012

By
Sunhwa Kim  and
Michael Karin
Edited by
David Lyden ,
Danny R. Welch  and
Bethan Psaila
Sunhwa Kim
Affiliation:
University of Pittsburgh School of Medicine, United States
Michael Karin
Affiliation:
University of California, San Diego, United States
David Lyden
Affiliation:
Weill Cornell Medical College, New York
Danny R. Welch
Affiliation:
Weill Cornell Medical College, New York
Bethan Psaila
Affiliation:
Imperial College of Medicine, London
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Summary

EXTRINSIC VERSUS INTRINSIC MEDIATORS OF INFLAMMATION

A link between chronic inflammation and cancer has been suspected since the nineteenth century, when Rudolf Virchow first noted that malignant tumors arise at regions of chronic inflammation and contain inflammatory infiltrates [1–5]. However, the sources of inflammation in tumors that are not associated with a chronic inflammation remain incompletely understood. Recently, it became apparent that inflammation can be evoked not only by extrinsic mediators but also by intrinsic mediators (endogenous molecules) (Figure 14.1). For instance, it has been established that necrotic cell death results in the release of molecules normally stored within cells, such as high-mobility group box 1 (HMGB1) and interleukin (IL)-1α, that act as potent inflammatory mediators [6, 7]. Such molecules may responsible for the triggering of tumor-associated inflammation [7].

Toll-like receptors (TLRs), the mammalian homologs of the Drosophila Toll protein, play a crucial role in activation of inflammatory responses and innate host defenses against invading microorganisms by their ability to recognize conserved molecular motifs of microbial origin, also known as pathogen-associated molecular patterns (PAMs) [8–10]. A number of intrinsic mediators have been shown to be capable of engaging TLR family members and other innate immune receptors and thereby trigger the activation of myeloid and lymphoid cells as well as stimulate the maturation of dendritic cells (DCs) [6, 11–13].

The first mammalian TLR to be identified, TLR4, is the receptor for lipopolysaccharide (LPS), a major cell wall component of Gram-negative bacteria [10].

Type
Chapter
Information
Cancer Metastasis
Biologic Basis and Therapeutics
 , pp. 155 - 166
Publisher: Cambridge University Press
Print publication year: 2011

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