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Carcinoma Cell Hyaluronan as a “Portable” Cancerized Prometastatic Microenvironment

Turley, Eva A., Wood, David K., McCarthy, James B.·2016·Cancer Research
DOI 10.1158/0008-5472.can-15-3114PMC PMC4874571
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Abstract

Hyaluronan (HA) is a structurally simple polysaccharide, but its ability to act as a template for organizing pericellular matrices and its regulated synthesis and degradation are key to initiating repair responses. Importantly, these HA functions are usurped by tumor cells to facilitate progression and metastasis. Recent advances have identified the functional complexities associated with the synthesis and degradation of HA-rich matrices. Three enzymes synthesize large HA polymers while multiple hyaluronidases or tissue free radicals degrade these into smaller bioactive fragments. A family of extracellular and cell-associated HA-binding proteins/receptors translates the bioinformation encrypted in this complex polymer mixture to activate signaling networks required for cell survival, proliferation, and migration in an actively remodeling microenvironment. Changes in HA metabolism within both the peritumor stroma and parenchyma are linked to tumor initiation, progression, and poor clinical outcome. We review evidence that metastatic tumor cells must acquire the capability to autonomously synthesize, assemble, and process their own “portable” HA-rich microenvironments to survive in the circulation, metastasize to ectopic sites, and escape therapeutic intervention. Strategies to disrupt the HA machinery of primary tumor and circulating tumor cells may enhance the effectiveness of current conventional and targeted therapies. Cancer Res; 76(9); 2507–12. ©2016 AACR.

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Metadata

Authors
Turley, E. A., Wood, D. K., & McCarthy, J. B.
Affiliations
  • 1Cancer Research Laboratories, London Regional Cancer Center, Victoria Hospital, London, Ontario, Canada.
  • 3Department of Biomedical Engineering, College of Science and Engineering, University of Minnesota, Minneapolis, Minnesota.
  • 4Masonic Cancer Center, Minneapolis, Minnesota.
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2016-05-01
Volume
76
Issue
9
Pages
2507-2512
ISSN
  • 0008-5472
  • 1538-7445
DOI
10.1158/0008-5472.can-15-3114
PMC
PMC4874571
Cited by
71
References
2
Language
en

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