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 three tasks. First, the cDNA for hum HA synthase (HAS3) was cloned and transfected into TSU causing them to over-express HA. The resulting cells grew faster than 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 HAS 3, which caused them to express reduced levels of HA. These cells were found to grow slower than their control transfected counter-parts. And thirdly, we examined the effects of hyaluronidase on the growth of tumor xenografts on the chorioallantoic membranes of chicken embryos. Contrary to our expectations, hyaluronidase caused an increase in the size of the xenografts due part to the induction of hemorrhages. This suggests that HA plays a role in maintaining the structural integrity of the blood vessels. Collectively, these results support our working hypothesis that HA promotes tumor progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA412824
Entities
People
- Charles B. Underhill
Organizations
- Georgetown University