Prostate cancer increases hyaluronan in surrounding nonmalignant stroma, and this response is associated with tumor growth and an unfavorable outcome

Am J Pathol. 2011 Oct;179(4):1961-8. doi: 10.1016/j.ajpath.2011.06.005. Epub 2011 Aug 18.


Our objective was to investigate whether the presence of a tumor increases hyaluronan (HA) levels in surrounding prostate tissues and whether this extratumoral HA influences tumor growth and outcome. From a series of 287 men diagnosed with prostate cancer at transurethral resection and followed up with watchful waiting, tissue microarrays were constructed, stained, and scored for HA. A high HA staining score in the tumor stroma or in nonmalignant prostate tissue stroma were both associated positively with higher Gleason score and larger tumor volume, and was associated with a poor outcome. HA staining score was not an independent marker for outcome (multivariate Cox, with Gleason score, tumor volume, stage, and HA variables). In an orthotopic rat prostate cancer model, hyaluronic acid synthase-1 mRNA levels and HA staining were increased in normal prostate tissue surrounding prostate cancer. Orthotopic prostate cancer growth was increased by intraprostatic injection of HA. In conclusion, cancer in the prostate apparently stimulates HA synthesis both in tumor stroma and in the surrounding normal tissue. This promoted tumor growth and was associated with an unfavorable outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Biomarkers, Tumor / metabolism
  • Cell Proliferation
  • Glucuronosyltransferase / metabolism
  • Humans
  • Hyaluronan Synthases
  • Hyaluronic Acid / metabolism*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prostate / metabolism
  • Prostate / pathology
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Rats
  • Staining and Labeling
  • Stromal Cells / metabolism
  • Stromal Cells / pathology
  • Treatment Outcome
  • Watchful Waiting


  • Biomarkers, Tumor
  • Hyaluronic Acid
  • Glucuronosyltransferase
  • HAS1 protein, human
  • Hyaluronan Synthases