Poster Presentation 29th Lorne Cancer Conference 2017

Vitamin D differentially regulates gene expression of heparanase in tumour cells (#162)

Shaun Gaskin 1 , Mark Hulett 1
  1. La Trobe University, Bundoora, VIC, Australia

Cancer is the leading cause of death worldwide, with 90% of deaths caused by metastasis. Tumour cells undergoing metastasis must invade the extracellular matrix, which provides structural support and acts as a ‘reservoir’ for signalling molecules. Approximately 17 extracellular matrix macromolecules are heparan sulfate proteoglycans. Cleavage of heparan sulfate chains occurs exclusively via the endo-β-glucoronidase heparanase. Increased expression of heparanase is observed in essentially all cancers, and results in a decrease in patient survival, with heparanase expression linked to larger tumour mass, increased tumour cell invasion and metastatic events. It has previously been shown that heparanase is also implicated in the development of proteinuria. Using a glomerular disease model, active vitamin D, 1,25-dihydroxyvitamin D3, was shown to provide protection from proteinuria formation by increasing vitamin D receptor binding to the heparanase promoter, consequently decreasing expression of heparanase. Initial investigation into the effect of active vitamin D on MDA-MB-231 human breast cancer cells indicates that treatment increases expression of heparanase mRNA. In contrast, treatment of B16F10 mouse melanoma cells causes a decrease in heparanase mRNA expression, providing evidence of differences in the regulation of the heparanase promoter in these cell types. Understanding the role of active vitamin D in heparanase expression and identifying the differences in the heparanase promoter between human and mouse may lead to more effective strategies to prevent tumour metastasis, increasing the rates of cancer patient survival.