HAS1 expression in bladder cancer and its relation to urinary HA test

Roozbeh Golshani, Stefan H. Hautmann, Veronica Estrella, Brian L. Cohen, Christopher C. Kyle, Murugesan Manoharan, Merce Jorda, Mark S. Soloway, Vinata B. Lokeshwar

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30 Scopus citations

Abstract

Hyaluronic acid (HA) levels are elevated in bladder cancer tissues and regulate tumor growth and progression. Urinary HA levels measured by the HA test are an accurate marker for bladder cancer. In cells, HA is synthesized by one of the 3 HA-synthase(s) i.e., HAS1, HAS2 and HAS3. In this study, we examined HASl expression in bladder cancer cells and tissues. Real-time RT-PCR and northern blot analyses showed that HASl transcript levels are elevated 5- to 10-fold in bladder cancer tissues, when compared with normal tissues (p < 0.001). Among the 3 HAS1 splice variants, only HAS1-va was expressed in bladder tissues, but the expression was significantly lower than the wild type HAS1 transcript. Increased HASl expression in bladder tumor tissues correlated with increased tissue HA levels (p < 0.001). Size of the large HA species (2.0 × 106 D) present in bladder tissues was consistent with the size of the HA polymer synthesized by HAS1. The amount of HA produced by bladder cancer cell lines correlated with the expression of HAS1 protein. Immunohistochemical analyses of bladder tumor tissues showed that HAS1 and HA expression had 79-88% sensitivity and 83.3-100% specificity. Both HASl and HA expression in bladder cancer tissues correlated with a positive HA urine test (p < 0.001). HASl expression correlated with tumor recurrence, prior treatment (p < 0.05) and possibly disease progression (p = 0.058). Therefore, elevated HASl expression in bladder tumor tissues contributes to a positive HA urine test and may have some prognostic potential.

Original languageEnglish (US)
Pages (from-to)1712-1720
Number of pages9
JournalInternational Journal of Cancer
Volume120
Issue number8
DOIs
StatePublished - Apr 15 2007

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Keywords

  • Bladder cancer
  • HA test
  • HA-synthase
  • HAS1
  • Hyaluronic acid

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Golshani, R., Hautmann, S. H., Estrella, V., Cohen, B. L., Kyle, C. C., Manoharan, M., Jorda, M., Soloway, M. S., & Lokeshwar, V. B. (2007). HAS1 expression in bladder cancer and its relation to urinary HA test. International Journal of Cancer, 120(8), 1712-1720. https://doi.org/10.1002/ijc.22222