Dataset Information

Hyaluronic acid family in bladder cancer: potential prognostic biomarkers and therapeutic targets.

ABSTRACT:

Background

Molecular markers of clinical outcome may aid in designing targeted treatments for bladder cancer. However, only a few bladder cancer biomarkers have been examined as therapeutic targets.

Methods

Data from The Cancer Genome Atlas (TCGA) and bladder specimens were evaluated to determine the biomarker potential of the hyaluronic acid (HA) family of molecules - HA synthases, HA receptors and hyaluronidase. The therapeutic efficacy of 4-methylumbelliferone (4MU), a HA synthesis inhibitor, was evaluated in vitro and in xenograft models.

Results

In clinical specimens and TCGA data sets, HA synthases and hyaluronidase-1 levels significantly predicted metastasis and poor survival. 4-Methylumbelliferone inhibited proliferation and motility/invasion and induced apoptosis in bladder cancer cells. Oral administration of 4MU both prevented and inhibited tumour growth, without dose-related toxicity. Effects of 4MU were mediated through the inhibition of CD44/RHAMM and phosphatidylinositol 3-kinase/AKT axis, and of epithelial-mesenchymal transition determinants. These were attenuated by HA, suggesting that 4MU targets oncogenic HA signalling. In tumour specimens and the TCGA data set, HA family expression correlated positively with β-catenin, Twist and Snail expression, but negatively with E-cadherin expression.

Conclusions

This study demonstrates that the HA family can be exploited for developing a biomarker-driven, targeted treatment for bladder cancer, and 4MU, a non-toxic oral HA synthesis inhibitor, is one such candidate.

SUBMITTER: Morera DS

PROVIDER: S-EPMC5680466 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Publications

Hyaluronic acid family in bladder cancer: potential prognostic biomarkers and therapeutic targets.

Morera Daley S DS Hennig Martin S MS Talukder Asif A Lokeshwar Soum D SD Wang Jiaojiao J Garcia-Roig Michael M Ortiz Nicolas N Yates Travis J TJ Lopez Luis E LE Kallifatidis Georgios G Kramer Mario W MW Jordan Andre R AR Merseburger Axel S AS Manoharan Murugesan M Soloway Mark S MS Terris Martha K MK Lokeshwar Vinata B VB

British journal of cancer 20171003 10

<h4>Background</h4>Molecular markers of clinical outcome may aid in designing targeted treatments for bladder cancer. However, only a few bladder cancer biomarkers have been examined as therapeutic targets.<h4>Methods</h4>Data from The Cancer Genome Atlas (TCGA) and bladder specimens were evaluated to determine the biomarker potential of the hyaluronic acid (HA) family of molecules - HA synthases, HA receptors and hyaluronidase. The therapeutic efficacy of 4-methylumbelliferone (4MU), a HA synth ...[more]

PMID: 28972965

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Dataset Information

Hyaluronic acid family in bladder cancer: potential prognostic biomarkers and therapeutic targets.

Background

Methods

Results

Conclusions

Publications

Hyaluronic acid family in bladder cancer: potential prognostic biomarkers and therapeutic targets.

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