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Cancers 2012, 4(3), 873-903; doi:10.3390/cancers4030873

Therapeutic Targeting of Hyaluronan in the Tumor Stroma

1
Department of Research, Halozyme Therapeutics, 11388 Sorrento Valley Road, San Diego, CA 92121, USA
2
Department of Pharmacology and Safety Assessment, Halozyme Therapeutics, 11388 Sorrento Valley Road, San Diego, CA 92121, USA
3
Department of General and Administrative, Halozyme Therapeutics, 11388 Sorrento Valley Road, San Diego, CA 92121, USA
*
Author to whom correspondence should be addressed.
Received: 25 June 2012 / Revised: 28 August 2012 / Accepted: 31 August 2012 / Published: 6 September 2012
(This article belongs to the Special Issue Tumor Stroma)
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Abstract

The tumor stroma, consisting of non-malignant cells and the extracellular matrix, undergoes significant quantitative and qualitative changes throughout malignant transformation and tumor progression. With increasing recognition of the role of the tumor microenvironment in disease progression, stromal components of the tumor have become attractive targets for therapeutic intervention. Stromal accumulation of the glycosaminoglycan hyaluronan occurs in many tumor types and is frequently associated with a negative disease prognosis. Hyaluronan interacts with other extracellular molecules as well as cellular receptors to form a complex interaction network influencing physicochemical properties, signal transduction, and biological behavior of cancer cells. In preclinical animal models, enzymatic removal of hyaluronan is associated with remodeling of the tumor stroma, reduction of tumor interstitial fluid pressure, expansion of tumor blood vessels and facilitated delivery of chemotherapy. This leads to inhibition of tumor growth and increased survival. Current evidence shows that abnormal accumulation of hyaluronan may be an important stromal target for cancer therapy. In this review we highlight the role of hyaluronan and hyaluronan-mediated interactions in cancer, and discuss historical and recent data on hyaluronidase-based therapies and the effect of hyaluronan removal on tumor growth.
Keywords: cancer; tumor stroma; hyaluronan; hyaluronidase; PEGPH20 cancer; tumor stroma; hyaluronan; hyaluronidase; PEGPH20
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Kultti, A.; Li, X.; Jiang, P.; Thompson, C.B.; Frost, G.I.; Shepard, H.M. Therapeutic Targeting of Hyaluronan in the Tumor Stroma. Cancers 2012, 4, 873-903.

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