Format

Send to

Choose Destination
Semin Cancer Biol. 2019 Aug 11. pii: S1044-579X(19)30237-8. doi: 10.1016/j.semcancer.2019.07.026. [Epub ahead of print]

Danger matrix molecules orchestrate CD14/CD44 signaling in cancer development.

Author information

1
Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Goethe University, Frankfurt am Main, Germany.
2
Translational Hepatology, Department of Internal Medicine I, University Clinic Frankfurt, Germany.
3
Department of Biochemistry, Faculty of Medicine, Universities of Giessen and Marburg Lung Center, Giessen, Germany.
4
Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Goethe University, Frankfurt am Main, Germany. Electronic address: Schaefer@med.uni-frankfurt.de.

Abstract

The tumor matrix together with inflammation and autophagy are crucial regulators of cancer development. Embedded in the tumor stroma are numerous proteoglycans which, in their soluble form, act as danger-associated molecular patterns (DAMPs). By interacting with innate immune receptors, the Toll-like receptors (TLRs), DAMPs autonomously trigger aseptic inflammation and can regulate autophagy. Biglycan, a known danger proteoglycan, can regulate the cross-talk between inflammation and autophagy by evoking a switch between pro-inflammatory CD14 and pro-autophagic CD44 co-receptors for TLRs. Thus, these novel mechanistic insights provide some explanation for the plethora of reports indicating that the same matrix-derived DAMP acts either as a promoter or suppressor of tumor growth. In this review we will summarize and critically discuss the role of the matrix-derived DAMPs biglycan, hyaluronan, and versican in regulating the TLR-, CD14- and CD44-signaling dialogue between inflammation and autophagy with particular emphasis on cancer development.

KEYWORDS:

Biglycan; Hyaluronan; Inflammation; Toll-like receptor; Versican

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center