Yin and Yang of Heparanase in Breast Tumor Initiation
Abstract
Heparanase (HPR1) is an endoglycosidase that specifically degrades heparan sulfate proteoglycans, a main constituent on the cell surface and in the extracellular matrix and basement membrane. The role of heparanase in breast cancer tumorigenesis remains unclear. In particular, whether HPR1 enzymatic activity is required for its stimulatory effect on tumor growth and initiation are not fully understood. Our earlier study showed that the C-terminus of HPR1, which lacks the enzymatic activity, was able to accelerate breast cancer formation in a somatic breast cancer mouse model since mice infected with RCAS-Neu virus plus RCAS-8C (a vector encoding the C terminus of HPR1), developed breast cancer significantly faster than that infected with RCAS-Neu plus RCAS-GFP (Green fluorescence protein) control virus. Here we report that the similar observations were made with PyMT oncogene-induced breast cancer, e.g. co-infection with RCAS-PyMT virus plus RCAS-8C virus induced breast cancer significantly faster than RCAS-PyMT virus plus RCAS-GFP. Enzymatically dead HPR1 had similar effect in stimulating breast cancer formation in the C-terminus of HPR1. In contrast, co-infection of TVA transgenic mice with RCAS-PyMT virus plus RCAS-HPR1 virus significantly delayed breast cancer formation than those infected with RCAS-PyMT virus plus RCAS-GFP control virus. Our results strongly suggest that HPR1 promotes tumor growth independent of its enzymatic activity, and that the enzymatic activity of HPR1 antagonizes the tumor initiating activity of HPR1.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2014
- Accession Number
- ADA600915
Entities
People
- Xiulong Xu
Organizations
- Rush University