Emerging roles for hyaluronidase in cancer metastasis and therapy

Caitlin O. McAtee, Joseph J. Barycki, Melanie A. Simpson

Research output: Contribution to journalArticlepeer-review

153 Scopus citations


Hyaluronidases are a family of five human enzymes that have been differentially implicated in the progression of many solid tumor types, both clinically and in functional studies. Advances in the past 5 years have clarified many apparent contradictions: (1) by demonstrating that specific hyaluronidases have alternative substrates to hyaluronan (HA) or do not exhibit any enzymatic activity, (2) that high-molecular weight HA polymers elicit signaling effects that are opposite those of the hyaluronidase-digested HA oligomers, and (3) that it is actually the combined overexpression of HA synthesizing enzymes with hyaluronidases that confers tumorigenic potential. This review examines the literature supporting these conclusions and discusses novel mechanisms by which hyaluronidases impact invasive tumor cell processes. In addition, a detailed structural and functional comparison of the hyaluronidases is presented with insights into substrate selectivity and potential for therapeutic targeting. Finally, technological advances in targeting hyaluronidase for tumor imaging and cancer therapy are summarized.

Original languageEnglish (US)
Pages (from-to)1-34
Number of pages34
JournalAdvances in Cancer Research
StatePublished - 2014


  • Cancer therapy
  • Hyaluronan
  • Hyaluronidase
  • Metastasis
  • Tumor biology
  • Tumor imaging

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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