Pericellular Hyaluronan and Prostate Cancer
Abstract
The working hypothesis of the present project is that hyaluronan (HA) promotes tumor growth by maintaining pericellular spaces that allows the diffusion of nutrients. To test this hypothesis, we have carried out the following specific aims. First, the cDNA for human HA synthase 3 (HAS3) was cloned and transfected into TSU (human prostate cancer) causing them to over-express HA. The resulting cells were found to grow faster under both in vitro and in vivo conditions, as compared to the control cells. In addition, histological examination of the tumors indicated that the HAS3 transfectants had increased intercellular space rich in HA and had greater number of blood vessels. Secondly, TSU cells were transfected with anti-sense vectors to HAS3, which caused them to express reduced levels of HA. These cells were found to grow slower than their control transfected counter-parts. These results supported our original working hypothesis that expression of HA promoted tumor cell growth. And thirdly, when tumor cells were transfected with expression vectors for hyaluronidase, they were found to increase their growth rate. We believe that this final result is due to the release of growth factors such as FGF from the extracellular matrix.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA400558
Entities
People
- Charles B. Underhill
Organizations
- Georgetown University